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Influence of methanandamide and CGRP on potassium currents in smooth muscle cells of small mesenteric arteries

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bol, Mélissa Leybaert, Luc Vanheel, Bert
Description	Country affiliation: Belgium Author Affiliation: Bol M ( Physiology Group, Department of Basic Medical Sciences, Ghent University, UZ blok B, De Pintelaan 185, 9000, Ghent, Belgium.)
Abstract	Cannabinoids have potent vasodilatory actions in a variety of vascular preparations. Their mechanism of action, however, is complex. Apart from acting on vascular smooth muscle or endothelial cannabinoid receptors, several studies point to the activation of type 1 vanilloid (TRPV1) receptors on primary afferent perivascular nerves, stimulating the release of calcitonin gene-related peptide (CGRP). In the present study, the direct influence of the cannabinoid methanandamide and the neuropeptide CGRP on the membrane potassium ion $(K^{+})$ currents of rat mesenteric myocytes was explored. Methanandamide (10 μM) decreased outward $K^{+}$ currents, an effect similar to that observed in smooth muscle cells from the rat aorta. Conversely, CGRP (10 nM) significantly increased whole-cell $K^{+}$ currents and this effect was abolished by preexposure to tetraethylammonium chloride (1 mM) or iberiotoxin (100 nM), inhibitors of large-conductance calcium-dependent K $(BK_{Ca})$ channels but not by glibenclamide (10 μM), an inhibitor of ATP-dependent K channels. In the presence of the CGRP receptor antagonist $CGRP_{8-37}$ (100 nM), the adenylyl cyclase inhibitor SQ22536 (100 μM), or the protein kinase A inhibitor Rp-cAMPS (10 μM), CGRP had no effect. These findings show that methanandamide does not increase membrane $K^{+}$ currents in smooth muscle cells of small mesenteric arteries, supporting an indirect mechanism for the reported hyperpolarizing influence in this vessel. Moreover, CGRP acts directly on these smooth muscle cells by increasing $BK_{Ca}$ channel activity in a CGRP receptor and cyclic adenosine monophosphate-dependent way. Collectively, these data indicate that methanandamide relaxes and hyperpolarizes intact mesenteric vessels by releasing CGRP from perivascular nerves.
File Format	HTM / HTML
ISSN	00316768
Issue Number	5
Volume Number	463
e-ISSN	14322013
Journal	Pflügers Archiv - European Journal of Physiology
Language	English
Publisher	Springer
Publisher Date	2012-04-01
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Physiology Arachidonic Acids Pharmacology Calcitonin Gene-related Peptide Metabolism Mesenteric Arteries Drug Effects Myocytes, Smooth Muscle Potassium Adenylyl Cyclase Inhibitors Adenylate Cyclase Animals Aorta Physiology Cyclic Amp Cyclic Amp-dependent Protein Kinases Antagonists & Inhibitors Female Large-conductance Calcium-activated Potassium Channels Membrane Potentials Muscle Cells Muscle, Smooth, Vascular Rats Rats, Wistar Receptors, Calcitonin Gene-related Peptide Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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