TRPV1 receptor: a target for the treatment of pain, cough, airway disease and urinary incontinence.
The TRPV1 channel is mainly expressed in sensory nerves. Activation of the channel induces neuropeptide release from central and peripheral sensory nerve terminals, resulting in the sensation of pain, neurogenic inflammation, smooth muscle contraction and cough. The TRPV1 channel can be activated by vanilloids such as capsaicin, as well as endogenous stimulators including H(+), heat, lipoxygenase products and anandamide. TRPV1 channel function is upregulated by several endogenous mediators present in inflammatory conditions, which decreases the threshold for activation of the channel. Under these conditions, TRPV1 can be activated by physiological body temperature, slight acidification or lower concentration of TRPV1 agonists. There is evidence that TRPV1 plays a role in the development of pathophysiological changes and symptoms in several diseases. In this review, we discuss TRPV1 channel activation and regulation in normal and diseased conditions, the role of TRPV1 in pain, cough, asthma and urinary incontinence, and the potential use of TRPV1 antagonists as a novel therapy for these diseases.
Jia
Yanlin
Y
Pulmonary and Peripheral Neurobiology, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. yanlin.jia@spcorp. com
McLeod
Robbie L
RL
Hey
John A
JA
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D003371:Cough / Q000188:drug therapy* / Q000209:etiology; D063388:Endocannabinoids; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D008084:Lipoxygenase / Q000494:pharmacology; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000209:etiology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D007473:Ion Channels; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D008084:Lipoxygenase; C078814:anandamide