The anandamide transport inhibitor AM404 activates vanilloid receptors.
The possibility that the anandamide transport inhibitor N-(4-hydroxyphenyl)-5,8,11,14-eicosatetraenamide (AM404), structurally similar to the vanilloid receptor agonists anandamide and capsaicin, may also activate vanilloid receptors and cause vasodilation was examined. AM404 evoked concentration-dependent relaxations in segments of rat isolated hepatic artery contracted with phenylephrine. Relaxations were abolished in preparations pre-treated with capsaicin. The calcitonin-gene related peptide (CGRP) receptor antagonist CGRP-(8-37) also abolished relaxations. The vanilloid receptor antagonist capsazepine inhibited vasodilation by AM404 and blocked AM404-induced currents in patch-clamp experiments on Xenopus oocytes expressing the vanilloid subtype 1 receptor (VR1). In conclusion, AM404 activates native and cloned vanilloid receptors.
Zygmunt
P M
PM
Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University, SE-221 85, Lund, Sweden. peter.zygmunt@klinfarm.lu.se
Chuang
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H
Movahed
P
P
Julius
D
D
Högestätt
E D
ED
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D063388:Endocannabinoids; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D014664:Vasodilation / Q000187:drug effects; D014981:Xenopus
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D010446:Peptide Fragments; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D011955:Receptors, Drug; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; D000077285:Rimonabant; D002211:Capsaicin; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide