mandag den 11. februar 2013

Transient Receptor Potential in Multiple Chemical Sensitivity

I have previously written about Transient Receptor Potential Ion Channels, because they are mentioned in research on ME/CFS and co-morbid conditions.

TRP is also involved in chemosensation and maybe in Multiple Chemical Sensitivity (MSC).

TRPA1/TRPV1 in chemosensation

Transient Receptor Potential Ankyrin 1 (TRPA1) is a member of the TRP family. TRPA1 function as a sensory neuronal TRP ion channel, in airway chemosensation and inflammation. TRPA1 is activated by chlorine, reactive oxygen species and noxious constituents of smoke and smog, initiating irritation and airway reflex responses.

Together with Transient Receptor Potential Vanilloid 1 (TRPV1), TRPA1 may contribute to chemical hypersensitivity, chronic cough and airway inflammation in asthma.

Trigeminal chemosensory nerve endings in the nasal mucosa are in the first line of defense against noxious chemical challenges.

TRPA1 is expressed in 20–36.7 percent of trigeminal neurons, 20–56.5 percent of dorsal root ganglion neurons, and 28.4 percent of neurons in nodose ganglia.

Neuropeptides such as Substance P and Calcitonin Gene Related Peptide (CGRP), released from chemically stimulated nerve endings, promote neurogenic inflammatory vasodilation and leakage, contributing to narrowing or obstruction of the nasal passages.

Since most TRPA1 agonist can react with thiols, cellular and extracellular reduced glutathione levels will affect the reach and potency of inhaled airway irritants. Once glutathione is depleted, either as a consequence of disease or during extended exposures, TRPA1 may respond much more strongly. With each breath more reactive agonist is delivered, leading to an increase in covalent modifications and heightened TRPA1 activity. This cumulative effect may result in robust TRPA1-induced irritation even at low sub-acute exposure levels, for example during periods of increased photochemical smog exposures, or low level indoor air pollution. Once irreversibly modified, channels may remain active for extended periods of time even when the irritant stimulus is removed.

(I think it is interesting that TRPA1 reacts more strongly when glutathione is depleted, because a study found decreased levels of cortical glutathione in CFS patients )

Reference: Breathtaking TRP Channels: TRPA1 and TRPV1 in Airway Chemosensation and Reflex Control

Reference: Chapter 11 TRPA1 : A Sensory Channel of Many Talents

Research on this topic is to be found in the Project Reporter from National Insitutes of Health

Project Leader Gerry Oxford has this project:

“Increased exposure to chemical irritants in the air we breathe may be responsible for the increased incidence of migraine as well as more recently described disorders such as Sick building syndrome (SBS) and Multiple Chemical Sensitivity (MCS).”

“It has been demonstrated that a member of the transient receptor potential (TRP) superfamily of ligand-gated ion channels, TRPA1, is activated by a novel mechanism involving covalent interaction between many chemicals and the receptor-channel leading to excitation of sensory neurons expressing TRPA1 and elevations in intracellular calcium.In this proposal, we will examine a specific hypothesis linking inhaled chemical irritants to the induction of headache symptoms. We propose that chemical activation of TRPA1 homomers, or TRPA1/TRPV1 heteromers on trigeminal neurons innervating the meninges results in release of calcitonin gene-related peptide (CGRP), a potent vasodilator implicated in migraine. The resultant vasodilatation provokes headache symptoms.”

The knowledge about TRPA1 is used in a patent application:
Treatment of Respiratory Disorders using TRPA1 Antagonists

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