title: Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro.
abstract: The effect of anandamide, which activates both the cannabinoid 1 (CB1) receptor and the vanilloid receptor 1 (VR1), was studied on calcitonin gene-related peptide (CGRP) release from cultured primary sensory neurons, the majority of which coexpress the CB1 receptor and VR1. Concentrations of anandamide < 1 micro m produced a small but significant CB1 receptor-mediated inhibition of basal CGRP release while higher concentrations induced VR1-mediated CGRP release. The excitatory effect of anandamide was potentiated by the CB1 receptor antagonist SR141716A. In the presence of SR141716A at concentrations < 100 nm, anandamide was equipotent with capsaicin in stimulating CGRP release. However, at higher concentrations anandamide produced more CGRP release than equimolar concentrations of capsaicin. Three and ten nanomolar anandamide inhibited the capsaicin-evoked CGRP release. In the presence of SR141716A, treatments which activated protein kinase A, protein kinase C and phospholipase C significantly potentiated the anandamide-evoked CGRP release at all anandamide concentrations. Although this potentiation was reduced when the CB1 receptor antagonist was omitted from the buffer, the CGRP release evoked by 300 nm and 1 micro m anandamide was still significantly larger than that seen with nonpotentiated cells. These data indicate that anandamide may regulate CGRP release from capsaicin-sensitive primary sensory neurons in vivo, and that the net effect of anandamide on transmitter release from capsaicin-sensitive primary sensory neurons depends on the concentration of anandamide and the state of the CB1 receptor and VR1. These findings also suggest that anandamide could be one of the molecules responsible for the development of inflammatory heat hyperalgesia.
authors.affiliation: Department of Academic Anaesthetics, Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: Laszlo
authors.initials: L
authors.lastname: Urban
authors.forename: Stuart
authors.initials: S
authors.lastname: Bevan
authors.forename: Istvan
authors.initials: I
authors.lastname: Nagy
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D063388:Endocannabinoids; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D020932:Nerve Growth Factor / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism*; D000077285:Rimonabant; D050916:TRPV Cation Channels; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D005576:Colforsin; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide