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

Mélissa Bol (UGent) , Luc Leybaert (UGent) and Bert Vanheel (UGent)
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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 mu M) 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 (BKCa) channels but not by glibenclamide (10 mu M), 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 mu M), or the protein kinase A inhibitor Rp-cAMPS (10 mu M), 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 BKCa 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.
Keywords
Vasoactive agents, Cannabinoids, Endothelial factors, Vasorelaxation, Vanilloid receptor, Neuropeptides, GENE-RELATED PEPTIDE, PORCINE CORONARY-ARTERY, SENSORY NERVES MEDIATE, PROTEIN-KINASE-A, CANNABINOID RECEPTOR, RAT AORTA, HYPERPOLARIZING FACTOR, VANILLOID RECEPTORS, INDUCED RELAXATION, GASTRIC ARTERIES

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Chicago
Bol, Mélissa, Luc Leybaert, and Bert Vanheel. 2012. “Influence of Methanandamide and CGRP on Potassium Currents in Smooth Muscle Cells of Small Mesenteric Arteries.” Pflugers Archiv-european Journal of Physiology 463 (5): 669–677.
APA
Bol, M., Leybaert, L., & Vanheel, B. (2012). Influence of methanandamide and CGRP on potassium currents in smooth muscle cells of small mesenteric arteries. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 463(5), 669–677.
Vancouver
1.
Bol M, Leybaert L, Vanheel B. Influence of methanandamide and CGRP on potassium currents in smooth muscle cells of small mesenteric arteries. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY. 2012;463(5):669–77.
MLA
Bol, Mélissa, Luc Leybaert, and Bert Vanheel. “Influence of Methanandamide and CGRP on Potassium Currents in Smooth Muscle Cells of Small Mesenteric Arteries.” PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY 463.5 (2012): 669–677. Print.
@article{2106370,
  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 mu M) 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 (BKCa) channels but not by glibenclamide (10 mu M), 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 mu M), or the protein kinase A inhibitor Rp-cAMPS (10 mu M), 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 BKCa 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.},
  author       = {Bol, M{\'e}lissa and Leybaert, Luc and Vanheel, Bert},
  issn         = {0031-6768},
  journal      = {PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY},
  keyword      = {Vasoactive agents,Cannabinoids,Endothelial factors,Vasorelaxation,Vanilloid receptor,Neuropeptides,GENE-RELATED PEPTIDE,PORCINE CORONARY-ARTERY,SENSORY NERVES MEDIATE,PROTEIN-KINASE-A,CANNABINOID RECEPTOR,RAT AORTA,HYPERPOLARIZING FACTOR,VANILLOID RECEPTORS,INDUCED RELAXATION,GASTRIC ARTERIES},
  language     = {eng},
  number       = {5},
  pages        = {669--677},
  title        = {Influence of methanandamide and CGRP on potassium currents in smooth muscle cells of small mesenteric arteries},
  url          = {http://dx.doi.org/10.1007/s00424-012-1083-1},
  volume       = {463},
  year         = {2012},
}

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