Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonic Acids / metabolism*
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Arachidonic Acids / pharmacology*
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Calcitonin Gene-Related Peptide / pharmacology
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Cannabinoids / metabolism*
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Capsaicin / pharmacology
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Endocannabinoids
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Female
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Hepatic Artery / drug effects
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In Vitro Techniques
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Oocytes / drug effects
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Oocytes / metabolism
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Patch-Clamp Techniques
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Peptide Fragments / pharmacology
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Piperidines / pharmacology
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Polyunsaturated Alkamides
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Pyrazoles / pharmacology
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Rats
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Rats, Wistar
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Receptors, Drug / agonists*
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Receptors, Drug / antagonists & inhibitors
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Rimonabant
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Vasodilation / drug effects
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Xenopus
Substances
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Arachidonic Acids
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Cannabinoids
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Endocannabinoids
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Peptide Fragments
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Piperidines
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Polyunsaturated Alkamides
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Pyrazoles
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Receptors, Drug
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calcitonin gene-related peptide (8-37)
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Calcitonin Gene-Related Peptide
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Rimonabant
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Capsaicin
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anandamide
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N-(4-hydroxyphenyl)arachidonylamide