TRPA1 og Multiple Chemical Sensitivity

Jeg har tidligere skrevet om TRPA1 og MCS: Transient Receptor Potential in Multiple Chemical Sensitivity

Og jeg har gættet på et lille forsøg, som kunne være interessant: Kan mRNA for TRPA1 benyttes som biomarkør for MCS?

Og nu fandt jeg lige ud af, at andre længe før mig har haft lignende tanker, dog ikke i forbindelse med MCS, men i forbindelse med Gulf War Illness (GWI). Disse krigsveteraner har været eksponeret for mange kemikalier og en stor del af dem har udviklet kemikalieoverfølsomhed. Professor Bruce Zuraw er manden bag et forsøg med titlen Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness

Han vil finde ud af om TRPV1 og TRPA1 er opreguleret hos GWI veteraner og om dette kan anvendes i forbindelse med en biomarkør. I forsøgsbeskrivelsen kan man læse følgende:

"We propose that the respiratory symptoms of subjects with GWI is caused in part by enhanced airway sensitivity to irritants, mediated primarily by upregulated or sensitized TRP channels in the airway. We have now shown that transformed and primary airway epithelial cells express functional TRPV1. More recently we found that these cells also express another important irritant receptor, namely TRPA1. Activation of either TRPV1 or TRPA1 results in increased expression of both the inflammatory cytokine IL-8 and the neurotrophin NGF in airway epithelial cells. We have further shown that NGF as well as bradykinin and CCL5 can sensitize TRPV1, lower the activation threshold, and enhance the inflammatory consequences of agonist stimulation. The combination of sensitized TRPV1 channels that have a lower threshold for activation from common irritants combined with TRP activation-mediated synthesis of NGF leading to further sensitization of sensory afferents and epithelial cells suggests a mechanism by which non-specific airway sensitivity may be initiated and sustained in a self-perpetuating manner."

og længere nede:

"As detailed above, we have developed sensitive real-time RT-PCR assays for mRNA transcripts of these genes, including TRPV1, TRPA1, the bradykinin B2 and B1 receptors, the entire range of neurotrophin receptors, and the cannabinoid receptor, CNR2. We still need to design and test primers for the tachykinin receptors."

Jeg tror  næppe, at aktiverede TRPV1 og TRPA1 receptorer (målt ved mRNA eller ander metoder) kan stå alene som biomarkør for respiratoriske problemer eller MCS. Men sammen med andre parametre kunne det være en mulighed. Under alle omstændigheder er det forsøg som disse, der vil kaste mere lys på biokemien bag ved sygdomme som GWI og MCS.

Andre forskere spekulerer allerede i hvordan respiratoriske tilstande, herunder MCS, kan behandles med TRPA1 antagonister. Se denne patentansøgning:

PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT

"The present patent application relates to a pharmaceutical composition comprising a transient receptor potential ankyrin-1 receptor ("TRPA1") antagonist and an anticholinergic agent. Particularly, the application provides a pharmaceutical composition comprising a TRPA1 antagonist having IC₅₀ for inhibiting human TRPA1 receptor activity of less than 1 micromolar and an anticholinergic agent; a process for preparing such composition; and its use in treating a respiratory disorder in a subject."

"The respiratory disorder, in the context of present invention, includes but is not limited to airway inflammation, asthma, emphysema, bronchitis, COPD, sinusitis, rhinitis, cough, respiratory depression, reactive airways dysfunction syndrome (RADS), acute respiratory distress syndrome (ARDS), irritant induced asthma, occupational asthma, sensory hyper-reactivity, multiple chemical sensitivity, and aid in smoking cessation therapy."