Temperature-dependent activation of recombinant rat vanilloid VR1 receptors expressed in HEK293 cells by capsaicin and anandamide.
Capsaicin activates vanilloid (VR1) receptors found on sensory neurons. These ligand-gated ion channels are also sensitive to low pH, elevated temperature and the endocannabinoid, anandamide. In this study, we have measured capsaicin- and anandamide-induced elevations in intracellular calcium concentrations ([Ca(2+)](i)) in fura-2 loaded HEK293 cells stably expressing the rat VR1 receptor at 22, 37 and 50 degrees C. Both capsaicin and anandamide produced a concentration-dependent elevation in [Ca(2+)](i) at all temperatures. pEC(50) values were 7.74 and 5.69 at 22 degrees C and 6.90 and 5.15 at 37 degrees C for capsaicin and anandamide, respectively. At 50 degrees C, the pEC(50) value for capsaicin was 6.36 but the response to anandamide did not saturate. Responses to both agonists were sensitive to ruthenium red and capsazepine at all temperatures. This temperature-dependent reduction in potency may result from desensitization.
Sprague
J
J
University Department of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
Harrison
C
C
Rowbotham
D J
DJ
Smart
D
D
Lambert
D G
DG
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D015870:Gene Expression; D006801:Humans; D053284:Polyunsaturated Alkamides; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012430:Ruthenium Red / Q000494:pharmacology; D013696:Temperature
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug; D011994:Recombinant Proteins; D012430:Ruthenium Red; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium; C078814:anandamide