Xu S F, Collins M A, Chang K J
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Eur J Pharmacol. 1991 Aug 29;201(2-3):215-22. doi: 10.1016/0014-2999(91)90348-t.
The actions of tumor-promoting phorbol esters in smooth muscle excitation-contraction coupling were studied in isolated guinea pig ileum in the presence of various contractile agents. Muscarinic agonists, histamine and bradykinin elicited an initial transient phasic contraction and a subsequent sustained tonic contraction in guinea pig ileum. The Ca2+ channel antagonist nifedipine selectively inhibited the tonic contraction. Phorbol esters, protein kinase C activators, induced immediate muscle relaxation followed by oscillatory contractions when added during the tonic phase of contraction. Phorbol esters, when added in advance, slightly altered the ligand-induced phasic contraction but converted tonic contractions into oscillatory spikes. The amplitude, frequency and shape of the oscillation induced by phorbol esters were dependent upon the dose of phorbol ester: amplitude was increased and frequency was decreased by increasing the doses of phorbol ester. In contrast, the phorbol ester potentiated the tonic contraction induced by high potassium chloride with little effect on the phasic component. It also sensitized the muscles to Bay K 8644. Bay K 8644, which was ineffective in stimulating muscle contraction at 1 nM, became a very effective stimulator in the presence of the phorbol ester. All of these phorbol ester-induced potentiations and oscillations were sensitive to inhibition by staurosporine or nifedipine. These data suggest that in guinea pig ileum, protein kinase C plays a positive regulatory role in Ca2+ channel activation and promotes a complex regulatory effect on Ca(2+)-mobilizing ligand-stimulated Ca2+ channel activity, which results in oscillatory contractile responses to carbachol, methacholine, histamine and bradykinin.
在存在各种收缩剂的情况下，在离体豚鼠回肠中研究了促肿瘤佛波酯在平滑肌兴奋-收缩偶联中的作用。毒蕈碱激动剂、组胺和缓激肽在豚鼠回肠中引发初始短暂的相性收缩和随后持续的强直性收缩。钙通道拮抗剂硝苯地平选择性抑制强直性收缩。佛波酯（蛋白激酶C激活剂）在收缩的强直期加入时，会立即引起肌肉松弛，随后出现振荡性收缩。预先加入佛波酯时，会轻微改变配体诱导的相性收缩，但会将强直性收缩转变为振荡性尖峰。佛波酯诱导的振荡的幅度、频率和形状取决于佛波酯的剂量：增加佛波酯的剂量会使幅度增加而频率降低。相反，佛波酯增强了高氯化钾诱导的强直性收缩，对相性成分影响很小。它还使肌肉对Bay K 8644敏感。在1 nM时对刺激肌肉收缩无效的Bay K 8644，在存在佛波酯的情况下变成了非常有效的刺激剂。所有这些佛波酯诱导的增强作用和振荡对星形孢菌素或硝苯地平的抑制敏感。这些数据表明，在豚鼠回肠中，蛋白激酶C在钙通道激活中起正向调节作用，并对钙动员配体刺激的钙通道活性产生复杂的调节作用，这导致对卡巴胆碱、乙酰甲胆碱、组胺和缓激肽产生振荡性收缩反应。
