Kimura S, Koide Y, Tada R, Abe K, Ogata E
Endocrinol Jpn. 1981 Feb;28(1):69-78. doi: 10.1507/endocrj1954.28.69.
In an attempt to verify the importance of calcium ions in mediating alpha -adrenergic stimulation, the effects of a calcium channel blocker, verapamil, on phenylephrine-induced glycogenolysis and calcium efflux in perfused livers prepared from fed rats were determined. The blocker inhibited phenylephrine-induced glycogenolysis in a noncompetitive and dose-dependent manner between 50 micro M and 500 micro M. However, it did not affect 2, 4-dinitrophenol-induced glycogenolysis. It had no significant effect on 45 Ca uptake by the perfused liver, but inhibited basal as well as phenylephrine-induced efflux of 45Ca from 45Ca-loaded liver. The inhibitory effects on basal 45Ca release and phenylephrine-induced glycogenolysis and 45Ca released correlated very well. All the 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. These results indicate that the process of calcium influx and the function of phosphorylase per se are not directly involved in the inhibitory action of the blocker. Although it is possible that verapamil interferes with binding of the alpha -adrenergic agonist to the plasma membrane, the good correlation between the inhibitory effects of verapamil on basal 45Ca released and on phenylephrine-induced release of 45Ca 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.
为了验证钙离子在介导α-肾上腺素能刺激中的重要性，测定了钙通道阻滞剂维拉帕米对由喂食大鼠制备的灌注肝脏中去氧肾上腺素诱导的糖原分解和钙流出的影响。该阻滞剂在50微摩尔至500微摩尔之间以非竞争性和剂量依赖性方式抑制去氧肾上腺素诱导的糖原分解。然而，它不影响2,4-二硝基苯酚诱导的糖原分解。它对灌注肝脏摄取45钙没有显著影响，但抑制了基础以及去氧肾上腺素诱导的45钙从45钙负载肝脏的流出。对基础45钙释放、去氧肾上腺素诱导的糖原分解和45钙释放的抑制作用相关性非常好。维拉帕米的所有作用都被另一种钙通道阻滞剂地尔硫卓重现，表明这些作用是各种钙通道阻滞剂共有的。这些结果表明钙内流过程和磷酸化酶本身的功能与该阻滞剂的抑制作用没有直接关系。虽然维拉帕米有可能干扰α-肾上腺素能激动剂与质膜的结合，但维拉帕米对基础45钙释放和去氧肾上腺素诱导的45钙释放的抑制作用之间的良好相关性提示了另一种涉及钙离子的机制。该阻滞剂似乎通过一种细胞膜机制抑制去氧肾上腺素诱导的糖原磷酸化酶活性，其中钙离子通量变化密切相关。
