Calcitonin gene-related peptide relaxes porcine coronary arteries via cyclic AMP-dependent mechanisms, but not activation of ATP-sensitive potassium channels

M. Kageyama, Teruyuki Yanagisawa, N. Taira

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We investigated the relaxant mechanisms of calcitonin gene-related peptide (CGRP) in endothelium-denuded porcine coronary arteries. Intracellular free calcium concentration ([Ca++](i)) was measured simultaneously with force by the fura-2 microfluorimetric method. CGRP (10-9 to 10-7 M) or isoproterenol (10-8 to 10-5 M) produced a concentration-dependent relaxation of arterial rings precontracted with 30 mM KCl with only a slight decrease in [Ca++](i). In contrast, cromakalim (3 x 10-7 to 3 x 10-5 M), an ATP-sensitive potassium channel opener, reduced [Ca++](i) and force in a parallel manner. When the arteries were precontracted with 90 mM KCl, the relaxant effects of CGRP and isoproterenol were attenuated, whereas that of cromakalim was abolished. In arteries precontracted with 90 mM KCl, reduction of extracellular calcium concentrations from 2.5 to 0.1 mM recovered the relaxant effects of CGRP and isoproterenol, but not that of cromakalim. All three relaxants reduced both [Ca++](i) and force in arteries precontracted with endothelin-1 (10-8M). Glibenclamide (10-5 M) inhibited the decrease in [Ca++](i) and the relaxation caused by cromakalim, but had virtually no effect on those produced by CGRP or isoproterenol. In arteries precontracted with 30 mM KCl and relaxed maximally by isoproterenol (10-5 M), CGRP (10-7 M) failed to produce any relaxant effect, whereas cromakalim (10-5 M) reduced [Ca++](i) and force further. The inhibitor of phosphodiesterase, 3-isobutyl-1-methylxanthine, potentiated the decreases in [Ca++](i) and relaxations caused by CGRP and isoproterenol, but not those by cromakalim. These results suggest that the CGRP-induced relaxation of porcine coronary arteries does not involve activation of ATP-sensitive potassium channels, but cyclic AMP-dependent mechanisms.

Original languageEnglish
Pages (from-to)490-497
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume265
Issue number2
Publication statusPublished - 1993 Nov 2

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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