title: TRPV1 is activated by both acidic and basic pH.
abstract: Maintaining physiological pH is required for survival, and exposure to alkaline chemicals such as ammonia (smelling salts) elicits severe pain and inflammation through unknown mechanisms. TRPV1, the capsaicin receptor, is an integrator of noxious stimuli including heat and extracellular acidic pH. Here, we report that ammonia activates TRPV1, TRPA1 (another polymodal nocisensor), and other unknown receptor(s) expressed in sensory neurons. Ammonia and intracellular alkalization activate TRPV1 through a mechanism that involves a cytoplasmic histidine residue, not used by other TRPV1 agonists such as heat, capsaicin or low pH. Our studies show that TRPV1 detects both acidic and basic deviations from homeostatic pH.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Dhaka
authors.forename: Valerie
authors.initials: V
authors.lastname: Uzzell
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Dubin
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mathur
authors.forename: Matt
authors.initials: M
authors.lastname: Petrus
authors.forename: Michael
authors.initials: M
authors.lastname: Bandell
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D000143:Acids / Q000494:pharmacology*; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002461:Cell Line, Transformed; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008164:Luminescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed / Q000379:methods; D018408:Patch-Clamp Techniques; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000187:drug effects*; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D000143:Acids; D008164:Luminescent Proteins; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D000643:Ammonium Chloride; D002211:Capsaicin; D002118:Calcium