RT Journal Article
SR Electronic
T1 Calcitonin gene-related peptide relaxes porcine coronary arteries via cyclic AMP-dependent mechanisms, but not activation of ATP-sensitive potassium channels.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 490
OP 497
VO 265
IS 2
A1 M Kageyama
A1 T Yanagisawa
A1 N Taira
YR 1993
UL http://jpet.aspetjournals.org/content/265/2/490.abstract
AB 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(-8) M). 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.(ABSTRACT TRUNCATED AT 250 WORDS)