Diamond J, Janis R A
Br J Pharmacol. 1980 Feb;68(2):275-82. doi: 10.1111/j.1476-5381.1980.tb10416.x.
1 The roles of guanosine cyclic 3',5'-monophosphate (cyclic GMP) and calcium in the relaxation produced by hydralazine and verapamil in potassium-depolarized guinea-pig taenia coli have been investigated.2 Depolarization of isolated strips of guinea-pig taenia coli by 124 mM KCl caused sustained contractures and increases in tissue levels of cyclic GMP.3 The KCl-induced increases in cyclic GMP levels appeared to be calcium dependent. No increases in cyclic GMP levels were seen in strips of taenia coli depolarized in the absence of calcium. Readdition of calcium to the depolarizing solution contracted the muscles and increased cyclic GMP levels. When calcium was removed from the depolarizing solution during the sustained, tonic phase of a KCl-induced contracture, both tension and cyclic GMP levels returned to control values.4 Administration of 50 muM verapamil to KCl-contracted muscles completely relaxed the muscles and caused cyclic GMP levels to return to control values within 14 min. Hydralazine, 2 mM, on the other hand, relaxed the depolarized muscles without lowering cyclic GMP levels. No significant changes in cyclic AMP levels were seen in any of these experiments.5 Similar results were obtained in an analogous series of experiments in which glycogen phosphorylase activity was measured instead of cyclic GMP levels. Activation of phosphorylase during contractions of guinea-pig taenia coli had previously been reported to be a calcium-dependent phenomenon.6 It was concluded that increases in tissue levels of cyclic GMP (or of cyclic AMP) were not responsible for the relaxant effects of hydralazine or verapamil in these experiments. It was also suggested, based on our results, that verapamil exerted its relaxant effects in the depolarized taenia coli by lowering cytoplasmic calcium levels, whereas hydralazine relaxed the depolarized muscles without lowering intracellular calcium activity.
1 研究了鸟苷环化3',5'-单磷酸（环磷酸鸟苷，cGMP）和钙在肼屈嗪和维拉帕米引起的豚鼠结肠带钾去极化舒张中的作用。
2 124 mM氯化钾使豚鼠结肠带分离条带去极化，导致持续挛缩并使组织中环磷酸鸟苷水平升高。
3 氯化钾诱导的环磷酸鸟苷水平升高似乎依赖于钙。在无钙条件下去极化的结肠带条带中未观察到环磷酸鸟苷水平升高。向去极化溶液中重新添加钙会使肌肉收缩并提高环磷酸鸟苷水平。在氯化钾诱导的挛缩的持续强直期，当从去极化溶液中去除钙时，张力和环磷酸鸟苷水平均恢复到对照值。
4 向氯化钾收缩的肌肉中给予50 μM维拉帕米可使肌肉完全舒张，并使环磷酸鸟苷水平在14分钟内恢复到对照值。另一方面，2 mM肼屈嗪可使去极化肌肉舒张，而不降低环磷酸鸟苷水平。在任何这些实验中均未观察到环磷酸腺苷水平有显著变化。
5 在一系列类似实验中获得了相似结果，在这些实验中测量糖原磷酸化酶活性而非环磷酸鸟苷水平。先前报道过豚鼠结肠带收缩期间磷酸化酶的激活是一种钙依赖性现象。
6 得出的结论是，在这些实验中，环磷酸鸟苷（或环磷酸腺苷）组织水平的升高并非肼屈嗪或维拉帕米舒张作用的原因。基于我们的结果还表明，维拉帕米通过降低细胞质钙水平在去极化的结肠带中发挥其舒张作用，而肼屈嗪使去极化肌肉舒张但不降低细胞内钙活性。
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