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: Scott M Rawls, Zhe Ding, Alan Cowan
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 83 Issue 4 Pg. 508-16 (Apr 2006) ISSN: 0091-3057 [Print] United States
• PMID: 16647109 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anilides
• Arachidonic Acids
• Cinnamates
• Endocannabinoids
• N-(3-methoxyphenyl)-4-chlorocinnamanilide
• Piperidines
• Polyunsaturated Alkamides
• Pyrazoles
• Receptor, Cannabinoid, CB1
• TRPV Cation Channels
• Trpv1 protein, rat
• Amidohydrolases
• fatty-acid amide hydrolase
• capsazepine
• Rimonabant
• Capsaicin
• anandamide
• N-(4-hydroxyphenyl)arachidonylamide

Topics

• Amidohydrolases (physiology)
• Anilides (pharmacology)
• Animals
• Arachidonic Acids (pharmacology)
• Body Temperature (drug effects)
• Capsaicin (analogs & derivatives, pharmacology)
• Cinnamates (pharmacology)
• Endocannabinoids
• Hypothermia (chemically induced)
• Male
• Piperidines (pharmacology)
• Polyunsaturated Alkamides
• Pyrazoles (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (physiology)
• Rimonabant
• TRPV Cation Channels (physiology)