MECHANISMS UNDERLYING THE INHIBITORY EFFECT OF DIBUTYRYL-CYCLIC-AMP IN VASCULAR SMOOTH-MUSCLE

被引:23
作者
ABE, A [1 ]
KARAKI, H [1 ]
机构
[1] UNIV TOKYO,FAC AGR,DEPT VET PHARMACOL,BUNKYO KU,TOKYO 113,JAPAN
关键词
SMOOTH MUSCLE (VASCULAR); AORTA; DIBUTYRYL CAMP; FURA-2-CA2+ SIGNAL; FORSKOLIN; CA2+ SENSITIVITY; (RAT);
D O I
10.1016/0014-2999(92)90385-H
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The mechanism by which dibutyryl cyclic AMP (db-cAMP) induces vasodilatation was examined in isolated rat aorta. The contraction induced by norepinephrine (NE) was more sensitive to the inhibitory effect of db-cAMP than that induced by high K+, and the contraction induced by lower concentrations of each stimulant was more sensitive to db-cAMP than that induced by higher concentrations. Db-cAMP at 10-mu-M inhibited the increases in muscle tension and cytosolic Ca2+ level ([Ca2+]i) without changing the [Ca2+]i-tension relationship, suggesting that the inhibitory effect is mainly due to a decrease in [Ca2+]i. A higher concentration (300-mu-M) of db-cAMP inhibited muscle tension more strongly than [Ca2+]i suggesting that db-cAMP decreases Ca2+ sensitivity of contractile elements. In contrast, 10-mu-M verapamil inhibited the NE-stimulated [Ca2+]i more strongly than the NE-induced contraction. The verapamil-insensitive portion of the NE-stimulated [Ca2+]i and contraction was inhibited by db-cAMP, suggesting that db-cAMP and verapamil act by different mechanisms. In Ca2+-free solution, 1-mu-M NE induced transient increases in muscle tension and [Ca2+]i. The transient contraction was inhibited by 1 mM db-cAMP more strongly than [Ca2+]i. An activator of adenylate cyclase, forskolin, showed inhibitory effects similar to those of db-cAMP. The inhibitory effects of db-cAMP and forskolin were inversely proportional to [Ca2+]i before the addition of these inhibitors. These results suggest that db-cAMP inhibits smooth muscle contraction by decreasing [Ca2+]i and the Ca2+sensitivity of contractile elements, and that both of these effects are stronger when [Ca2+]i is lower.
引用
收藏
页码:305 / 311
页数:7
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