title: Role of TRPV1 and cannabinoid CB1 receptors in AM 404-evoked hypothermia in rats.
abstract: AM 404 inhibits endocannabinoid uptake and enhances the cannabinoid CB(1)-mediated effects of endogenous cannabinoids. Accumulating evidence also suggests that AM 404 acts at sites other than the endocannabinoid system. One site is the transient receptor potential vanilloid 1 cation channel (TRPV1). A useful endpoint for discriminating between TRPV1- or CB(1)-mediated effects of AM 404 is hypothermia. This is because TRPV1 or CB(1) receptor activation produces a significant hypothermia in rats. The present study investigated the effects of AM 404 (1, 5, 10 and 20 mg/kg, i.p.) on body temperature in rats and the involvement of TRPV1 and CB(1) receptors in the effects of AM 404. Doses of 10 and 20 mg/kg of AM 404 produced significant hypothermia. Pre-treatment with capsazepine (30 mg/kg, i.p.) blocked the hypothermia caused by 10 and 20 mg/kg of AM 404. Pre-treatment with SB 366791 (2 mg/kg, i.p.), a new TRPV1 antagonist, also abolished the hypothermia evoked by AM 404 (20 mg/kg, i.p.). In contrast, pre-treatment with SR 141716A (Rimonabant), a CB(1) antagonist, or AA-5-HT, a fatty acid amide hydrolase (FAAH) blocker, did not affect AM 404-evoked hypothermia. The present data demonstrate that AM 404 evokes a significant hypothermia in rats that is dependent on TRPV1 receptor activation.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ding
authors.forename: Alan
authors.initials: A
authors.lastname: Cowan
mesh_terms: D000581:Amidohydrolases / Q000502:physiology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D063388:Endocannabinoids; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D000077285:Rimonabant; D050916:TRPV Cation Channels / Q000502:physiology*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000813:Anilides; D001095:Arachidonic Acids; D002211:Capsaicin; D002934:Cinnamates; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; C493922:Trpv1 protein, rat; C071423:capsazepine; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide