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Calcitonin gene-related peptide selectively relaxes contractile responses to endothelin-1 in rat mesenteric resistance arteries.
- Source :
- The Journal of Pharmacology and Experimental Therapeutics; October 2009, Vol. 331 Issue: 1 p87-95, 9p
- Publication Year :
- 2009
-
Abstract
- We tested the hypothesis that endothelin-1 (ET-1) modulates sensory-motor nervous arterial relaxation by prejunctional and postjunctional mechanisms. Isolated rat mesenteric resistance arteries were investigated with immunohistochemistry, wire-myography, and pharmacological tools. ET(A)- and ET(B)-receptors could be visualized on the endothelium and smooth muscle and on periarterial fibers containing calcitonin gene-related peptide (CGRP). Arterial contractile responses to ET-1 (0.25-16 nM) were not modified by blockade of ET(B)-receptors, NO-synthase, and cyclooxygenase or desensitization of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) with capsaicin. ET-1 reversed relaxing responses to CGRP in depolarized arteries. This effect was inhibited by ET(A)-antagonists. It was not selective because ET-1 also reversed relaxing responses to Na-nitroprusside (SNP) and because phenylephrine (PHE; 0.25-16 microM) similarly reversed relaxing responses to CGRP or SNP. Conversely, contractile responses to ET-1 were, compared with PHE, hypersensitive to the relaxing effects of the TRPV1-agonist capsaicin and to exogenous CGRP, but not to acetylcholine, forskolin, pinacidil, or SNP. In conclusion, ET-1 does not stimulate sensory-motor nervous arterial relaxation, but ET(A)-mediated arterial contractions are selectively sensitive to relaxation by the sensory neurotransmitter CGRP. This does not involve NO, cAMP, or ATP-sensitive K(+) channels.
Details
- Language :
- English
- ISSN :
- 00223565 and 15210103
- Volume :
- 331
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- The Journal of Pharmacology and Experimental Therapeutics
- Publication Type :
- Periodical
- Accession number :
- ejs20139433
- Full Text :
- https://doi.org/10.1124/jpet.109.155143