TRPA1 er en receptor, som bl.a. findes i luftvejene og i celler i hjernen. TRPA1 indgår i mange sammenhænge, f.eks. bliver den aktiveret af kemikalier i forbindelse med advarsel/oprydning i kroppen. Forskellige kemiske forbindelser, f.eks. røg, fungerer som agonist til receptoren. Dvs de kemiske forbindelser aktiverer eller ”tænder” for receptoren.
Her har jeg oversat en passage fra denne artikel:
Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control
”For ethvert given kemikalie vil TRPA1 agonist aktivitet afhænge af den reversible eller irreversible karakter af de kemiske dannede bindinger og på agonist membran permeabilitet. Da de fleste TRPA1 agonister kan reagere med thioler, vil cellulære og ekstracellulære reduceret glutathion-niveauer påvirker rækkevidde og styrken af inhalerede luftvejs irritanter. Når glutathion er opbrugt, enten som følge af sygdom eller ved længere eksponeringer, kan TRPA1 reagere langt stærkere. Med hvert åndedrag er mere reaktiv agonist leveret, hvilket fører til en stigning i kovalente ændringer og øget TRPA1 aktivitet. Denne kumulative effekt kan resultere i en robust TRPA1-induceret irritation selv ved lave sub-akutte eksponering niveaurt, for eksempel i perioder med øget fotokemisk smog, eller ved lavt niveau af indendørs luftforurening. Når de først er irriversibelt ændret, kan kanaler forblive aktiv i længere tid, selv når irriterende stimulus er fjernet.”
På godt dansk: Når vi indånder kemiske forbindelser, som er giftige for os, vil TRPA1 blive aktiveret, og der er brug for et stof, glutathion, til at rydde op. Når kroppen ikke kan følge med i dannelse af glutathion, så er vi lidt på den.
Det gælder så for alle mennesker, men hvad med mennesker med ME og MCS?
Det viser sig, at ME patienter mangler glutathion i hjernen, og at en del MCS patienter har ringere evne til "at rydde op med glutathion".
Det var da en pudsig sammenhæng mellem ME, MCS, TRPA1 og glutathion – sammen med alle de andre pudsige sammenhænge, som man kan læse om på min blog.
Nu er det her kun ”en lille bid” af en større biokemisk sammenhæng ( i en forenklet forklaring), men hvis man begyndte at kæde tingene sammen, kunne man måske løse gåden om ME/POTS/MCS/smerter, og hvordan det hele hang sammen.
mandag den 17. februar 2014
TRPA1 som sensor for ilt – kan det have betydning for ME?
Jeg har rejst spørgsmålet om en dysregulering af receptoren TRPA1 er del af ætiologien bag ME. Og i min sidste blogpost gættede jeg på mulige mekanismer.
Der er endnu en god grund til at mistænke TRPA1 for at være en medspiller i ME. Post exertional malaise (PEM) og iltoptagelse i ME er kerneområder, der undersøges og diskuteres i sygdommen. Og TRPA1 kan også agere som ilt sensor og advarer om for meget og for lidt ilt (hyperoxia og hypoxia).
Peter Zygmont har skrevet en fremragende lille artikel om emnet, Channels: A TR(i)P in the air
Ikke alene gennemgås det, hvordan TRPA1 aktiveres både af hyperoxia og hypoxia, men han nævner også receptorens relevans for bl. a. migræne, irritable bowel disease (IBS), blære hyperaktivitet og fibromyalgi.
Mange af de sygdomme, som jeg nævner på min blog og som jeg sætter i forbindelse med TRPA1, kaldes i Danmark også for funktionelle lidelser. Det kan undre mig, at i et land som Danmark, hvor der anvendes to-cifrede millionbeløb på forskning i funktionelle lidelser, at jeg slet ikke kan finde noget om TRPA1.
Der er endnu en god grund til at mistænke TRPA1 for at være en medspiller i ME. Post exertional malaise (PEM) og iltoptagelse i ME er kerneområder, der undersøges og diskuteres i sygdommen. Og TRPA1 kan også agere som ilt sensor og advarer om for meget og for lidt ilt (hyperoxia og hypoxia).
Peter Zygmont har skrevet en fremragende lille artikel om emnet, Channels: A TR(i)P in the air
Ikke alene gennemgås det, hvordan TRPA1 aktiveres både af hyperoxia og hypoxia, men han nævner også receptorens relevans for bl. a. migræne, irritable bowel disease (IBS), blære hyperaktivitet og fibromyalgi.
Mange af de sygdomme, som jeg nævner på min blog og som jeg sætter i forbindelse med TRPA1, kaldes i Danmark også for funktionelle lidelser. Det kan undre mig, at i et land som Danmark, hvor der anvendes to-cifrede millionbeløb på forskning i funktionelle lidelser, at jeg slet ikke kan finde noget om TRPA1.
Hvorfor indgår TRPA1 receptoren i så mange sammenhænge – og indgår den i ME?
Jeg har i tidligere blogposts angivet receptoren TRPA1, som en mulig indgående (dysreguleret) faktor i både POTS, MCS, smerter mm. Nu er TRPA1 bare en lille brik i et større biokemisk puslespil, hvor mange andre faktorer indgår. For at forstå hvordan en enkelt receptor kan være så mangfoldig, er man nødt til at forstå, hvad der påvirker den. Førend TRPA1 bliver aktiveret, kan der være indtruffet en række af biokemiske reaktioner.
Lad os kigge på et eksempel på, hvordan fornemmelsen af kløe opstår rent biokemisk. Her er TRPA1 også involveret. Så hvilken kæde af reaktioner fører til, at TRPA1 receptoren aktiveres og giver et signal?
I artiklen The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch findes en figur, der viser den biokemiske række af hændelser før TRPA1 aktiveres og sender besked op gennem rygraden til hjernen. (Klik ind og se figuren)
Som det fremgår af figuren er den en række af hændelser: PAR2 → ORAI1 → NFAT → TSLP → TSLP receptor → TRPA1.
Det er ikke af betydning i denne sammenhæng at forstå kæden af hændelser, men blot at forstå, at der ER en kæde af reaktioner.
Et andet eksempel er TRPA1s medvirken til smerte hypersensitivtet.
Klik ind på denne figur Model Depicting Functional Interactions between Bradykinin Receptors, TRPA1 and TRPV1.
Her ses rækken af biokemiske reaktioner (interaktioner) : Bradykinin receptoren påvirker TRPV1 receptoren, som igen påvirker TRPA1 receptoren.
Nu er det, at man skal tænke videre. Hvis TRPA1 også er involveret i ME, så kan TRPA1 måske i sig være dysreguleret eller den kan interagere med en receptor, der er dysreguleret.
Her er det værd at bemærke, at TRP receptorer ofte interagerer med receptorer, der kaldes G protein koblede receptorer
og
G protein koblede receptorer er ofte mål for autoimmune angreb.
Her kunne man måske tænke sig, at HVIS ME havde en autoimmun ætiologi, og HVIS dette var rettet mod en G protein koblet receptor, så kunne det MÅSKE forstyrre TRPA1.
Det kan naturligvis også være en hel anden mekanisme, - måske en mekansime, hvor der bliver ophobet en metabolit, som forstyrrer TRPA1.
Lad os kigge på et eksempel på, hvordan fornemmelsen af kløe opstår rent biokemisk. Her er TRPA1 også involveret. Så hvilken kæde af reaktioner fører til, at TRPA1 receptoren aktiveres og giver et signal?
I artiklen The Epithelial Cell-Derived Atopic Dermatitis Cytokine TSLP Activates Neurons to Induce Itch findes en figur, der viser den biokemiske række af hændelser før TRPA1 aktiveres og sender besked op gennem rygraden til hjernen. (Klik ind og se figuren)
Som det fremgår af figuren er den en række af hændelser: PAR2 → ORAI1 → NFAT → TSLP → TSLP receptor → TRPA1.
Det er ikke af betydning i denne sammenhæng at forstå kæden af hændelser, men blot at forstå, at der ER en kæde af reaktioner.
Et andet eksempel er TRPA1s medvirken til smerte hypersensitivtet.
Klik ind på denne figur Model Depicting Functional Interactions between Bradykinin Receptors, TRPA1 and TRPV1.
Her ses rækken af biokemiske reaktioner (interaktioner) : Bradykinin receptoren påvirker TRPV1 receptoren, som igen påvirker TRPA1 receptoren.
Nu er det, at man skal tænke videre. Hvis TRPA1 også er involveret i ME, så kan TRPA1 måske i sig være dysreguleret eller den kan interagere med en receptor, der er dysreguleret.
Her er det værd at bemærke, at TRP receptorer ofte interagerer med receptorer, der kaldes G protein koblede receptorer
og
G protein koblede receptorer er ofte mål for autoimmune angreb.
Her kunne man måske tænke sig, at HVIS ME havde en autoimmun ætiologi, og HVIS dette var rettet mod en G protein koblet receptor, så kunne det MÅSKE forstyrre TRPA1.
Det kan naturligvis også være en hel anden mekanisme, - måske en mekansime, hvor der bliver ophobet en metabolit, som forstyrrer TRPA1.
mandag den 10. februar 2014
TRPA1 and pain
An exciting new study about TRPA1 and pain:
Differential methylation of the TRPA1 promoter in pain sensitivity
References in relation to the paper:
Pain sensitivity may be influenced by lifestyle and environment
Derfor oplever enæggede tvillinger smerte forskelligt
Derfor føler eneggede tvillinger smerte forskjellig
..og lidt mere om TRPA1:
URMENNESKER GRÆD OGSÅ NÅR DE SKAR LØG
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?
TRP blogposts - an overview
Differential methylation of the TRPA1 promoter in pain sensitivity
References in relation to the paper:
Pain sensitivity may be influenced by lifestyle and environment
Derfor oplever enæggede tvillinger smerte forskelligt
Derfor føler eneggede tvillinger smerte forskjellig
..og lidt mere om TRPA1:
URMENNESKER GRÆD OGSÅ NÅR DE SKAR LØG
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?
TRP blogposts - an overview
Exercise followed by pain and exhaustion - is it ME?
Exercise, fasting and cold temperatures as triggers for pain episodes followed by exhaustion and deep sleep. The period of pain is accompanied by breathing difficulties, tachycardia and sweating. Is it Myalgic encephalomyelitis?
No, it is Gain-of-Function Mutation in TRPA1.
A point mutation in the S4 transmembrane segment of TRPA1, a key sensor for environmental
irritants, causes Familial Episodic Pain Syndrome. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials.
Check out the fine paper and video that explains the discovery:
A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome
TRP blogposts - an overview
No, it is Gain-of-Function Mutation in TRPA1.
A point mutation in the S4 transmembrane segment of TRPA1, a key sensor for environmental
irritants, causes Familial Episodic Pain Syndrome. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials.
Check out the fine paper and video that explains the discovery:
A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome
More about TRPA1:
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?TRP blogposts - an overview
fredag den 7. februar 2014
TRP blogposts - an overview
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?
TRPA1, LPS and the possible connection to ME symptoms
TRPA1 and migraine - ME and migraine
Excessive activation of TRPA1 and TRPV1 by ROS may induce central sensitization – does it concern ME?
TRPA1 og Multiple Chemical Sensitivity
A small peculiarity - ME, "ciguatoxin-look-alike" and TRPA1
Caveolae, eNOS and TRPA1?
Once again: TRPA1! Is activation of TRPA1 involved in ME?
Kan mRNA for TRPA1 benyttes som biomarkør for MCS?
Puslespilsbrikkerne: LPS, TLR4, TRPA1 og ME!?!
Vedvarende aktivering af TRPA1 og aflastning?
Variation i sensoriske reaktioner, TRP og stress
TRPA1, muskelaktivitet og påvirkning af det autonome nervesystem
ME, slow gastric emptying, serotonin and TRPA1
TRPA1, Hypoxia and ME?
Mitochondrial dysfunction - influence on TRPA1
Exercise and...TRPA1 and TRPV1
ME, neuropathy, TRPA1
TRPA1 involvement in autonomic dysfunction in ME?
TRPA1/TRPV4/PAR in inflammation/pain
Transient Receptor Potential in Multiple Chemical Sensitivity
TRP Ion Channels
TRPA1, LPS and the possible connection to ME symptoms
TRPA1 and migraine - ME and migraine
Excessive activation of TRPA1 and TRPV1 by ROS may induce central sensitization – does it concern ME?
TRPA1 og Multiple Chemical Sensitivity
A small peculiarity - ME, "ciguatoxin-look-alike" and TRPA1
Caveolae, eNOS and TRPA1?
Once again: TRPA1! Is activation of TRPA1 involved in ME?
Kan mRNA for TRPA1 benyttes som biomarkør for MCS?
Puslespilsbrikkerne: LPS, TLR4, TRPA1 og ME!?!
Vedvarende aktivering af TRPA1 og aflastning?
Variation i sensoriske reaktioner, TRP og stress
TRPA1, muskelaktivitet og påvirkning af det autonome nervesystem
ME, slow gastric emptying, serotonin and TRPA1
TRPA1, Hypoxia and ME?
Mitochondrial dysfunction - influence on TRPA1
Exercise and...TRPA1 and TRPV1
ME, neuropathy, TRPA1
TRPA1 involvement in autonomic dysfunction in ME?
TRPA1/TRPV4/PAR in inflammation/pain
Transient Receptor Potential in Multiple Chemical Sensitivity
TRP Ion Channels
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction...?
TRPs are part of the biochemistry in health and disease.
A role for TRPs in ME/CFS/POTS/MCS/pain/endothelial dysfunction... ? Can some of the symptoms be explained, if we understand the TRPs?
TRP Ion Channels – especially TRPA1 references:
Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [1]
Multiple Chemical Sensitivity (MCS), asthma and airways [12] , [13] , [14] , [15] , [16] , [17], [18] , [19] , [20] , [21], [22] , [23]
Irritable Bowel Syndrome (IBS) and gastrointestinal tract [24], [25] , [26] , [27] , [28] , [29] , [30] , [31], [32] , [33]
Reflux [34] , [35]
Pain – inflammation – central sensitization - neuropathy [36], [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46], [47] , [48] , [49] , [50], [51], [52], [53] , [54] , [55], [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64], [65]
LPS – bacterial endotoxin [66]
Endothelial function/dysfunction [67], [68] , [69] , [70] , [71] ,[72] , [73]
Vascular function [74] , [75] , [76] , [77] , [78] , [79] ,[80] , [81] , [82]
Regulation af cerebral blood flow [83] ,[84] , [85]
Migraine [86], [87] , [88] , [89] , [90]
Exercise [91] , [92] , [93] , [94] , [95]
Stress [96] , [97] , [98]
Hypoxia, sensors of oxygen [99] , [100] , [101] , [102] , [103] ,[104]
Mitochondria, redox, ROS, RNS [105] , [106] , [107] , [108], [109] , [110] , [111]
Glial cells[112]
Dorsal root ganglion [113] , [114]
Vagus nerve [115]
Spinal Cord Injury (SCI) [116]
Bladder pain syndrome/ bladder dysfunction [117], [118], [119] , [120] , [121] , [122] , [123]
Rosacea [124]
Analgesia [125], [126], [127] , [128] , [129] , [130]
TRP in disease [131], [132]
TRP in sensory transduction and cellular signaling [133], [134] , [135]
TRP projects [136] , [137] ,
TRP patent applications [138] , [139] , [140], [141] , [142]
Treatment [143] , [144]
Inhibition of TRPA1 [145]
[2] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo
[3] TRPA1 channels in the vasculature
[4] Transient receptor potential channels and vascular function
[5] Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow
[6] Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels
[7] TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation
[8] TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders
[9] Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)
[10] Redox Regulation of Endothelial Canonical Transient Receptor Potential Channels
[11] TRPA1 channels play a critical role in cold-induced vasodilatation
[12] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control
[13] Activation of Transient Receptor Potential Ankyrin-1 (TRPA1) in Lung Cells by Wood Smoke Particulate Material
[14] Pre-clinical studies in cough research: Role of Transient Receptor Potential (TRP) channels
[15] Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness
[16] Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons
[17] TRPA1 detects environmental chemicals and induces avoidance behavior and arousal from sleep
[18] Crucial Role of Transient Receptor Potential Ankyrin 1 and Mast Cells in Induction of Nonallergic Airway Hyperreactivity in Mice
[19] Transient receptor potential channels and occupational exposure
[20] Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells
[21] Pre-clinical studies in cough research: role of Transient Receptor Potential (TRP) channels
[22] A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma
[23] Multiple types of sensory neurons respond to irritating volatile organic compounds (VOCs): calcium fluorimetry of trigeminal ganglion neurons
[24] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain
[25] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain.
[26] QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells
[27] TRPA1 agonists delay gastric emptying in rats through serotonergic pathways
[28] TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells
[29] Psychological Co-morbidity in Functional Gastrointestinal Disorders: Epidemiology, Mechanisms and Management
[30] Sensory neuro-immune interactions differ between irritable bowel syndrome subtypes
[31] Acute Uterine Irritation Provokes Colonic Motility via Transient Receptor Potential A1-dependent Spinal NR2B Phosphorylation in Rats
[32] Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine
[33] Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain
[34] Airway Reflux, Cough and Respiratory Disease
[35] Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease
[36] Two to tango: GPCR oligomers and GPCR-TRP channel interactions in nociception.
[37] Role of Oxidative Stress and Ca(2+) Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels.
[38] TRPA1 Mediates Mechanical Sensitization in Nociceptors during Inflammation
[39] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control
[40] Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) Coupling is Required for Sustained Inflammatory Signaling
[41] Chemokines as Pain Mediators and Modulators
[42] Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy
[43] The dynamic TRPA1 channel: a suitable pharmacological pain target?
[44] Sustained TRPA1 activation in vivo
[45] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[46] TRPA1: A Transducer and Amplifier of Pain and Inflammation
[47] Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling
[48] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[49] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat
[50] Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice
[51] Sustained firing of TRPA1 elicited by reactive agonists
[52] Transient receptor potential A1 increase glutamate release on brain stem neurons
[53] TRPV1 and TRPA1 Mediate Peripheral Nitric Oxide-Induced Nociception in Mice
[54] Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors
[55] Sustained firing of TRPA1 elicited by reactive agonists
[56] Behavioral and Electrophysiological Study of Thermal and Mechanical Pain Modulation by TRP Channel Agonists
[57] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system
[58] Hypoxia-inducible Factor-1α (HIF1α) Switches on Transient Receptor Potential Ankyrin Repeat 1 (TRPA1) Gene Expression via a Hypoxia Response Element-like Motif to Modulate Cytokine Release
[59] Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation
[60] NGF up-regulates TRPA1: implications for orofacial pain
[61] Differential methylation of the TRPA1 promoter in pain sensitivity
[62] Neurotrophins, endocannabinoids and thermo-transient receptor potential: a threesome in pain signalling
[63] Modulation of Transient Receptor Vanilloid 1 Activity by Transient Receptor Potential
Ankyrin 1
[64] TRP-channels as key integrators of lipid pathways in nociceptive neurons
[65] Methylglyoxal Evokes Pain by Stimulating TRPA1
[66] TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
[67] TRP channels in endothelial function and dysfunction
[68] Expression and modulation of TRP channels in human microvascular endothelial cells
[69] Regulation and Function of TRPM7 in Human Endothelial Cells: TRPM7 as a Potential Novel Regulator of Endothelial Function
[70] Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels
[71] TRP channel Ca2+ sparklets: fundamental signals underlying endothelium-dependent hyperpolarization
[72] Model for TRPC5-mediated feedback of Ca2+ and NO signaling in endothelial cells and attenuation of Ca2+ entry through TRPC6 by NO in smooth muscle cells
[73] Cooperative Interaction of trp Melastatin Channel Transient Receptor Potential (TRPM2) With Its Splice Variant TRPM2 Short Variant Is Essential for Endothelial Cell Apoptosis
[74] Transient receptor potential channels and vascular function
[75] TRPA1 channels in the vasculature
[76] TRPV channels and vascular function
[77] TRP channels in vascular endothelial cells
[78] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo
[79] TRP channel and cardiovascular disease
[80] Transient Receptor Potential Channels in Cardiovascular Function and Disease
[81] Emerging concepts for the role of TRP channels in the cardiovascular system
[82] The NO/ONOO-cycle as the central cause of heart failure
[83] Endogenously-Generated Lipid Peroxidation Products Dilate Rat Cerebral Arteries by Activating TRPA1 Channels in the Endothelium
[84] TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS, VASCULARTONE AND AUTOREGULATION OF CEREBRAL BLOOD FLOW
[85] Proposed Signaling Pathway for TRPA1-Mediated Vasodilation of Cerebral Arteries
[86] TRPA1 and other TRP channels in migraine
[87] Activation of TRPA1 on dural afferents: a potential mechanism of headache pain
[88] Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel
[89] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system
[90] The TRPA1 Channel in Migraine Mechanism and Treatment
[91] Transient receptor potentials (TRPs) and anaphylaxis
[92] Muscle Afferent Receptors Engaged in Augmented Sympathetic Responsiveness in Peripheral Artery Disease
[93] Transient receptor potential A1 channel contributes to activation of the muscle reflex
[94] Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects
[95] Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls
[96] TRPV1 is a stress response protein in the central nervous system.
[97] Importance of TRP channels in pain: implications for stress
[98] Table 1. Cross-talk between several stress-related factors and TRP channels
[99] TRPA1 underlies a sensing mechanism for O2
[100] Reference: Channels: A TR(i)P in the air
[101] Reference: TRP channels: sensors and transducers of gasotransmitter signals
[102] Hypoxia-inducible factor-1α (HIF1α) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release
[103] Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1
[104] TRP channels as sensors of oxygen availability
[105] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
[106] Role of Reactive Oxygen Species and Redox in Regulating the Function of Transient Receptor Potential Channels
[107] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
[108] Redox Regulation of Transient Receptor Potential Channels
[109] Transnitrosylation Directs TRPA1 Selectivity in N-Nitrosamine Activators
[110] Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense anddanger
[111] Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress
[112] Pathophysiological roles of transient receptor potential channels in glial cells.
[113] Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse
[114] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[115] TRPV1, TRPA1, and CB1 in the isolated vagus nerve--axonal chemosensitivity and control of neuropeptide release
[116] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat
[117] Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: Implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.
[118] Mechanisms of Disease: involvement of the urothelium in bladder dysfunction
[119] THE ROLE OF TRPA1 CHANNELS IN ACTIVATION OF SINGLE UNIT MECHANOSENSITIVE BLADDER AFFERENT ACTIVITIES IN THE RAT
[120] TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury
[121] Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder
[122] Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia andurinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis
[123] Transient receptor potential channels in bladder function
[124] Neurovascular Aspects of Skin Neurogenic Inflammation
[125] TRPA1 as an Analgesic Target
[126] Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors
[127] Targeting TRP channels for pain relief
[128] TRP channels and analgesia
[129] Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents
[130] SuperPain—a resource on pain-relieving compounds targeting ion channels
[131] Transient receptor potential cation channels in disease.
[132] DYSREGULATED MRNAS MAY ALSO EXPLAIN COMMON CO-MORBIDITIES OF CFS
[133] TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades.
[134] Chapter 11 TRPA1 : A Sensory Channel of Many Talents
[135] The molecular basis for species-specific activation of human TRPA1 by protons involves poorly conserved residues within transmembrane domains 5 and 6
[136] ROLE OF TRP CHANNELS IN ENVIRONMENTAL IRRITANT-INDUCED HEADACHE DESCRIPTION
[137] POST-EXERCISE ION CHANNEL GENE EXPRESSION BIOMARKERS IN CFS
[138] NOVEL TRPA1 ANTAGONISTS
[139] Treatment of Respiratory Disorders using TRPA1 Antagonists
[140] PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT
[141] Heterocyclic amides as modulators of TRPA1
[142] Compounds useful for treating disorders related to TRPA1
[143] Modulation of TRP channels by resveratrol and other stilbenoids
[144] USE OF TRPA1 RECEPTOR ANTAGONISTS FOR TREATING DISEASES ASSOCIATED WITH BACTERIAL INFECTIONS
[145] Superpain database
TRP Ion Channels – especially TRPA1 references:
Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) [1]
Postural Orthostatic Tachycardia Syndrome (POTS) and vascular function [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9], [10], [11]
Multiple Chemical Sensitivity (MCS), asthma and airways [12] , [13] , [14] , [15] , [16] , [17], [18] , [19] , [20] , [21], [22] , [23]
Irritable Bowel Syndrome (IBS) and gastrointestinal tract [24], [25] , [26] , [27] , [28] , [29] , [30] , [31], [32] , [33]
Reflux [34] , [35]
Pain – inflammation – central sensitization - neuropathy [36], [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46], [47] , [48] , [49] , [50], [51], [52], [53] , [54] , [55], [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64], [65]
LPS – bacterial endotoxin [66]
Endothelial function/dysfunction [67], [68] , [69] , [70] , [71] ,[72] , [73]
Vascular function [74] , [75] , [76] , [77] , [78] , [79] ,[80] , [81] , [82]
Regulation af cerebral blood flow [83] ,[84] , [85]
Migraine [86], [87] , [88] , [89] , [90]
Exercise [91] , [92] , [93] , [94] , [95]
Stress [96] , [97] , [98]
Hypoxia, sensors of oxygen [99] , [100] , [101] , [102] , [103] ,[104]
Mitochondria, redox, ROS, RNS [105] , [106] , [107] , [108], [109] , [110] , [111]
Glial cells[112]
Dorsal root ganglion [113] , [114]
Vagus nerve [115]
Spinal Cord Injury (SCI) [116]
Bladder pain syndrome/ bladder dysfunction [117], [118], [119] , [120] , [121] , [122] , [123]
Rosacea [124]
Analgesia [125], [126], [127] , [128] , [129] , [130]
TRP in disease [131], [132]
TRP in sensory transduction and cellular signaling [133], [134] , [135]
TRP projects [136] , [137] ,
TRP patent applications [138] , [139] , [140], [141] , [142]
Treatment [143] , [144]
Inhibition of TRPA1 [145]
References:
[1] Translation from Mouse Sensory Neurons to Fibromyalgia and Chronic Fatigue Syndromes.[2] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo
[3] TRPA1 channels in the vasculature
[4] Transient receptor potential channels and vascular function
[5] Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow
[6] Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels
[7] TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation
[8] TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders
[9] Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)
[10] Redox Regulation of Endothelial Canonical Transient Receptor Potential Channels
[11] TRPA1 channels play a critical role in cold-induced vasodilatation
[12] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control
[13] Activation of Transient Receptor Potential Ankyrin-1 (TRPA1) in Lung Cells by Wood Smoke Particulate Material
[14] Pre-clinical studies in cough research: Role of Transient Receptor Potential (TRP) channels
[15] Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness
[16] Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons
[17] TRPA1 detects environmental chemicals and induces avoidance behavior and arousal from sleep
[18] Crucial Role of Transient Receptor Potential Ankyrin 1 and Mast Cells in Induction of Nonallergic Airway Hyperreactivity in Mice
[19] Transient receptor potential channels and occupational exposure
[20] Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells
[21] Pre-clinical studies in cough research: role of Transient Receptor Potential (TRP) channels
[22] A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma
[23] Multiple types of sensory neurons respond to irritating volatile organic compounds (VOCs): calcium fluorimetry of trigeminal ganglion neurons
[24] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain
[25] Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain.
[26] QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells
[27] TRPA1 agonists delay gastric emptying in rats through serotonergic pathways
[28] TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells
[29] Psychological Co-morbidity in Functional Gastrointestinal Disorders: Epidemiology, Mechanisms and Management
[30] Sensory neuro-immune interactions differ between irritable bowel syndrome subtypes
[31] Acute Uterine Irritation Provokes Colonic Motility via Transient Receptor Potential A1-dependent Spinal NR2B Phosphorylation in Rats
[32] Identification of enteroendocrine cells that express TRPA1 channels in the mouse intestine
[33] Effects of novel TRPA1 receptor agonist ASP7663 in models of drug-induced constipation and visceral pain
[34] Airway Reflux, Cough and Respiratory Disease
[35] Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease
[36] Two to tango: GPCR oligomers and GPCR-TRP channel interactions in nociception.
[37] Role of Oxidative Stress and Ca(2+) Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels.
[38] TRPA1 Mediates Mechanical Sensitization in Nociceptors during Inflammation
[39] Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control
[40] Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) Coupling is Required for Sustained Inflammatory Signaling
[41] Chemokines as Pain Mediators and Modulators
[42] Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy
[43] The dynamic TRPA1 channel: a suitable pharmacological pain target?
[44] Sustained TRPA1 activation in vivo
[45] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[46] TRPA1: A Transducer and Amplifier of Pain and Inflammation
[47] Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling
[48] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[49] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat
[50] Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice
[51] Sustained firing of TRPA1 elicited by reactive agonists
[52] Transient receptor potential A1 increase glutamate release on brain stem neurons
[53] TRPV1 and TRPA1 Mediate Peripheral Nitric Oxide-Induced Nociception in Mice
[54] Spinal 12-lipoxygenase-derived hepoxilin A3 contributes to inflammatory hyperalgesia via activation of TRPV1 and TRPA1 receptors
[55] Sustained firing of TRPA1 elicited by reactive agonists
[56] Behavioral and Electrophysiological Study of Thermal and Mechanical Pain Modulation by TRP Channel Agonists
[57] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system
[58] Hypoxia-inducible Factor-1α (HIF1α) Switches on Transient Receptor Potential Ankyrin Repeat 1 (TRPA1) Gene Expression via a Hypoxia Response Element-like Motif to Modulate Cytokine Release
[59] Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation
[60] NGF up-regulates TRPA1: implications for orofacial pain
[61] Differential methylation of the TRPA1 promoter in pain sensitivity
[62] Neurotrophins, endocannabinoids and thermo-transient receptor potential: a threesome in pain signalling
[63] Modulation of Transient Receptor Vanilloid 1 Activity by Transient Receptor Potential
Ankyrin 1
[64] TRP-channels as key integrators of lipid pathways in nociceptive neurons
[65] Methylglyoxal Evokes Pain by Stimulating TRPA1
[66] TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
[67] TRP channels in endothelial function and dysfunction
[68] Expression and modulation of TRP channels in human microvascular endothelial cells
[69] Regulation and Function of TRPM7 in Human Endothelial Cells: TRPM7 as a Potential Novel Regulator of Endothelial Function
[70] Endothelium-dependent cerebral artery dilation mediated by transient receptor potential and Ca2+-activated K+ channels
[71] TRP channel Ca2+ sparklets: fundamental signals underlying endothelium-dependent hyperpolarization
[72] Model for TRPC5-mediated feedback of Ca2+ and NO signaling in endothelial cells and attenuation of Ca2+ entry through TRPC6 by NO in smooth muscle cells
[73] Cooperative Interaction of trp Melastatin Channel Transient Receptor Potential (TRPM2) With Its Splice Variant TRPM2 Short Variant Is Essential for Endothelial Cell Apoptosis
[74] Transient receptor potential channels and vascular function
[75] TRPA1 channels in the vasculature
[76] TRPV channels and vascular function
[77] TRP channels in vascular endothelial cells
[78] Evidence for the pathophysiological relevance of TRPA1 receptors in the cardiovascular system in vivo
[79] TRP channel and cardiovascular disease
[80] Transient Receptor Potential Channels in Cardiovascular Function and Disease
[81] Emerging concepts for the role of TRP channels in the cardiovascular system
[82] The NO/ONOO-cycle as the central cause of heart failure
[83] Endogenously-Generated Lipid Peroxidation Products Dilate Rat Cerebral Arteries by Activating TRPA1 Channels in the Endothelium
[84] TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS, VASCULARTONE AND AUTOREGULATION OF CEREBRAL BLOOD FLOW
[85] Proposed Signaling Pathway for TRPA1-Mediated Vasodilation of Cerebral Arteries
[86] TRPA1 and other TRP channels in migraine
[87] Activation of TRPA1 on dural afferents: a potential mechanism of headache pain
[88] Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel
[89] Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system
[90] The TRPA1 Channel in Migraine Mechanism and Treatment
[91] Transient receptor potentials (TRPs) and anaphylaxis
[92] Muscle Afferent Receptors Engaged in Augmented Sympathetic Responsiveness in Peripheral Artery Disease
[93] Transient receptor potential A1 channel contributes to activation of the muscle reflex
[94] Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects
[95] Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls
[96] TRPV1 is a stress response protein in the central nervous system.
[97] Importance of TRP channels in pain: implications for stress
[98] Table 1. Cross-talk between several stress-related factors and TRP channels
[99] TRPA1 underlies a sensing mechanism for O2
[100] Reference: Channels: A TR(i)P in the air
[101] Reference: TRP channels: sensors and transducers of gasotransmitter signals
[102] Hypoxia-inducible factor-1α (HIF1α) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release
[103] Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1
[104] TRP channels as sensors of oxygen availability
[105] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
[106] Role of Reactive Oxygen Species and Redox in Regulating the Function of Transient Receptor Potential Channels
[107] Sensory Nerve Terminal Mitochondrial Dysfunction Activates Airway Sensory Nerves Via Transient Receptor Potential (TRP) Channels
[108] Redox Regulation of Transient Receptor Potential Channels
[109] Transnitrosylation Directs TRPA1 Selectivity in N-Nitrosamine Activators
[110] Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense anddanger
[111] Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress
[112] Pathophysiological roles of transient receptor potential channels in glial cells.
[113] Systematic and quantitative mRNA expression analysis of TRP channel genes at the single trigeminal and dorsal root ganglion level in mouse
[114] Reactive oxygen species enhance excitatory synaptic transmission in rat spinal dorsal horn neurons by activating TRPA1 and TRPV1 channels
[115] TRPV1, TRPA1, and CB1 in the isolated vagus nerve--axonal chemosensitivity and control of neuropeptide release
[116] Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat
[117] Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: Implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.
[118] Mechanisms of Disease: involvement of the urothelium in bladder dysfunction
[119] THE ROLE OF TRPA1 CHANNELS IN ACTIVATION OF SINGLE UNIT MECHANOSENSITIVE BLADDER AFFERENT ACTIVITIES IN THE RAT
[120] TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury
[121] Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder
[122] Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia andurinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis
[123] Transient receptor potential channels in bladder function
[124] Neurovascular Aspects of Skin Neurogenic Inflammation
[125] TRPA1 as an Analgesic Target
[126] Pharmacological blockade of TRPA1 inhibits mechanical firing in nociceptors
[127] Targeting TRP channels for pain relief
[128] TRP channels and analgesia
[129] Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as Emerging Target for Novel Analgesics and Anti-Inflammatory Agents
[130] SuperPain—a resource on pain-relieving compounds targeting ion channels
[131] Transient receptor potential cation channels in disease.
[132] DYSREGULATED MRNAS MAY ALSO EXPLAIN COMMON CO-MORBIDITIES OF CFS
[133] TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades.
[134] Chapter 11 TRPA1 : A Sensory Channel of Many Talents
[135] The molecular basis for species-specific activation of human TRPA1 by protons involves poorly conserved residues within transmembrane domains 5 and 6
[136] ROLE OF TRP CHANNELS IN ENVIRONMENTAL IRRITANT-INDUCED HEADACHE DESCRIPTION
[137] POST-EXERCISE ION CHANNEL GENE EXPRESSION BIOMARKERS IN CFS
[138] NOVEL TRPA1 ANTAGONISTS
[139] Treatment of Respiratory Disorders using TRPA1 Antagonists
[140] PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT
[141] Heterocyclic amides as modulators of TRPA1
[142] Compounds useful for treating disorders related to TRPA1
[143] Modulation of TRP channels by resveratrol and other stilbenoids
[144] USE OF TRPA1 RECEPTOR ANTAGONISTS FOR TREATING DISEASES ASSOCIATED WITH BACTERIAL INFECTIONS
[145] Superpain database
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