Low A M
Department of Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
Can J Physiol Pharmacol. 1996 Mar;74(3):298-304.
Recent evidence suggests that some Ca2+ channels are regulated by a tyrosine kinase pathway. The possibility that Ca2+ entry is regulated by tyrosine kinase was investigated in canine vascular muscles. Functional studies were carried out in the dog mesenteric arteries and saphenous veins. Nicardipine-insensitive refilling of phenylephrine-sensitive Ca2+ stores of endothelium-denuded dog mesenteric artery, previously depleted of Ca2+, measured after a 30-min exposure of the arterial rings to Ca2+ in the absence and presence of genistein (10-100 microM), tyrphostin 23 (10-100 microM), tyrphostin 47 (10-100 microM), SK&F 96365 (3-30 microM), or vehicle, DMSO, as phenylephrine contraction in Ca(2+)-free medium, decreased with increasing concentrations of the inhibitors compared with DMSO-treated and control. Phenylephrine contraction in Ca(2+)-free medium was not affected in a consistent manner by tyrosine kinase inhibitors when added after the store refilling period, in Ca(2+)-free medium, 5 min prior to stimulation with phenylephrine, indicating that the inhibitors have no effect on the Ca2+ release mechanism or that they act directly on myofilaments. Cyclopiazonic acid (30 microM), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, caused transient contractions in the dog saphenous vein only in the presence of extracellular Ca2+. These transient contractions were inhibited by tyrphostin 23 (30-100 microM), tyrphostin 47 (30-100 microM), genistein (30-100 microM), and SK&F 96365 (50-100 microM) but not by the vehicle DMSO. The results from this study provided evidence that a tyrosine kinase pathway is involved in the regulation of Ca2+ entry since inhibitors of tyrosine kinase are able to attenuate presumed Ca2+ entry following agonist-mediated Ca2+ store depletion. This route of Ca2+ entry is also sensitive to blockade by SK&F 96365.
最近的证据表明，一些钙离子通道受酪氨酸激酶途径调控。在犬类血管肌肉中研究了钙离子内流受酪氨酸激酶调控的可能性。在犬肠系膜动脉和隐静脉中进行了功能研究。在无钙和有染料木黄酮（10 - 100微摩尔）、 tyrphostin 23（10 - 100微摩尔）、 tyrphostin 47（10 - 100微摩尔）、SK&F 96365（3 - 30微摩尔）或溶剂二甲基亚砜（DMSO）存在的情况下，将动脉环暴露于钙离子30分钟后，测量去内皮犬肠系膜动脉对苯肾上腺素敏感的钙离子储存库尼卡地平不敏感的再充盈情况，该储存库先前已耗尽钙离子，与DMSO处理组和对照组相比，随着抑制剂浓度增加，在无钙培养基中作为苯肾上腺素收缩的情况减少。当在无钙培养基中苯肾上腺素刺激前5分钟的储存库再充盈期后添加酪氨酸激酶抑制剂时，无钙培养基中的苯肾上腺素收缩未受到一致影响，这表明抑制剂对钙离子释放机制无影响或它们直接作用于肌丝。环匹阿尼酸（30微摩尔），一种肌浆网钙离子泵抑制剂，仅在细胞外钙离子存在时在犬隐静脉中引起短暂收缩。这些短暂收缩受到tyrphostin 23（30 - 100微摩尔）、tyrphostin 47（30 - 100微摩尔）、染料木黄酮（30 - 100微摩尔）和SK&F 96365（50 - 100微摩尔）抑制，但不受溶剂DMSO抑制。本研究结果提供了证据，表明酪氨酸激酶途径参与钙离子内流的调控，因为酪氨酸激酶抑制剂能够减弱激动剂介导的钙离子储存库耗竭后推测的钙离子内流。这种钙离子内流途径也对SK&F 96365的阻断敏感。
