RT Journal Article
SR Electronic
T1 TRPV1 Is Activated by Both Acidic and Basic pH
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 153
OP 158
DO 10.1523/JNEUROSCI.4901-08.2009
VO 29
IS 1
A1 Ajay Dhaka
A1 Valerie Uzzell
A1 Adrienne E. Dubin
A1 Jayanti Mathur
A1 Matt Petrus
A1 Michael Bandell
A1 Ardem Patapoutian
YR 2009
UL http://www.jneurosci.org/content/29/1/153.abstract
AB 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.