Inhibitory effect of calcium channel blockers on .ALPHA.-adrenergic activation of glycogenolysis and calcium efflux in perfused rat liver.
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概要
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In an attempt to verify the importance of calcium ions in mediating α-adrenergic stimulation, the effects of a calcium channel blocker, verapamil, on phenylehrineinduced glycogenolysis and calcium efflux in perfused livers prepared from fed rats were determined.<BR>The blocker inhibited phenylephrine-induced glycogenolysis in a noncompetitive and dose-dependent manner between 50μM and 50μM. However, it did not affect 2, 4-dinitrophenol-induced glycogenolysis. It had no significant effect on <SUP>45</SUP> Ca uptake by the perfused liver, but inhibited basal as well as phenylephrine-induced efflux of <SUP>45</SUP>Ca from <SUP>45</SUP>Ca-loaded liver. The inhibitory effects on basal <SUP>45</SUP>Ca release and phenylephrine-induced glycogenolysis and <SUP>45</SUP>Ca release correlated very well. All of the effects of verapamil were reproduced by another calcium channel blocker, diltiazem, suggesting that these effects are common to a variety of calcium channel blockers.<BR>These results indicate that the process of calcium influx and the function of phosphorylase <I>per</I> se are not directly involved in the inhibitory action of the blocker. Although it is possible that verapamil interferes with binding of the α-adrenergic agonist to the plasma membrane, the good correlation between the inhibitory effects of verapamil on basal <SUP>45</SUP>Ca release and on phenylephrine-induced release of <SUP>45</SUP>Ca suggests another mechanism, involving calcium ions. The blocker appears to inhibit the glycogen phosphorylase activity induced by phenylephrine via a cell-membrane mechanism in which calcium ion flux changes are intimately involved.
- 社団法人 日本内分泌学会の論文
著者
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KIMURA SATOSHI
Endocrinology Division, National Cancer
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OGATA ETSURO
The Fourth Department of Medicine, Faculty of Medicine University of Tokyo
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Abe Kaoru
Endocrine Division National Cancer Center
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KOIDE YOSHINOBU
Institute of Clinical Medicine, University
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TADA RYOKO
Institute of Clinical Medicine, University of Tsukuba
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ABE KAORU
Endocrinology Division, National Cancer Center Research Institute
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OGATA ETSURO
The First Department of Internal Medicine, University of Tokyo
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KIMURA SATOSHI
Endocrinology Division, National Cancer Center Research Institute
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