Vasorelaxant effect of Win 55,212-2 in rat aorta: new mechanisms involved
| Autor: | M.I. Martin, Angela Alsasua, María Teresa Dannert, Esperanza Herradón, Visitación López-Miranda |
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| Rok vydání: | 2006 |
| Předmět: |
Agonist
Male medicine.medical_specialty Cannabinoid receptor Physiology medicine.drug_class medicine.medical_treatment Calcitonin Gene-Related Peptide Morpholines Vasodilator Agents TRPV Cation Channels Aorta Thoracic Pharmacology Calcitonin gene-related peptide GTP-Binding Protein alpha Subunits Gi-Go In Vitro Techniques Naphthalenes Nitric Oxide Biological Factors Internal medicine medicine Cannabinoid receptor type 2 Animals Rats Wistar Receptor WIN 55 212-2 Receptors Cannabinoid Dose-Response Relationship Drug Chemistry Receptor antagonist Benzoxazines Rats Vasodilation Endocrinology Prostaglandins Molecular Medicine Cannabinoid Endothelium Vascular medicine.drug |
| Zdroj: | Vascular pharmacology. 46(1) |
| ISSN: | 1537-1891 |
| Popis: | R (+)-[2,3-dihydro-5-methyl-3-[(moroholinyl)methyl] pyrrolo [1,2,3-de]-1,4benzoxazinyl]-1(1-naphthalenyl) methanone mesylate (Win 55,212-2) is a synthetic cannabinoid classically classified as a potent CB 1 and CB 2 agonist with high stereoselectivity and a slight preference for CB 2 cannabinoid receptors. Its vascular actions are not always explained by its binding to these cannabinoid receptors and new targets are being proposed. The aim of this study was to further assess the vascular actions of Win 55,212-2. Isometric tension changes in response to a cumulative concentration–response curve of Win 55,212-2 (10 − 9 M–10 − 4 M) were recorded in aortic rings from male Wistar rats. The involvement of the endothelium, cannabinoid receptors, vanilloid receptors, and the release of calcitonin gene related peptide (CGRP) was tested. Win 55,212-2 caused a concentration-dependent vasorelaxation in rat aorta. This vascular effect was significantly inhibited by endothelial denudation, inhibition of nitric oxide synthesis, a CB 1 receptor antagonist, a transient receptor potential vanilloid-1 antagonist, capsaicin desensibilization, and a CGRP receptor antagonist ( P 2 and non-CB 1 /non-CB 2 receptor antagonists only caused a slight inhibitory effect in vasorelaxation to Win 55,212-2. The present findings indicate that endothelium and nitric oxide-dependent vasorelaxation induced by Win 55,212-2 mainly involves vanilloid receptors while CB 1 , CB 2 and nonCB 1 /nonCB 2 cannabinoid receptors have a minor participation in its vascular effect. |
| Databáze: | OpenAIRE |
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