Patel J, Keith R A, Salama A I, Moore W C
ICI Americas Inc., Wilmington, DE 19897.
J Mol Neurosci. 1991;3(1):19-27. doi: 10.1007/BF02896845.
Using primary neuronal cultures we have examined the role of extracellular Ca2+ in a receptor-regulated phosphoinositide turnover. We report that receptor (glutamic acid and acetylcholine)-activated phosphoinositide turnover requires the presence of extracellular Ca2+ (EC50 = 21.1 microM). The requirement for Ca2+ appears to be at an intracellular level and is highly selective for Ca2+. We also found that several inorganic and organic Ca2+ channel blockers, including La3+ and verapamil, inhibit phosphoinositide turnover. However, the pharmacological profile of these agents in this regard was distinct from their actions at the voltage-sensitive Ca2+ channels. To explain the above requirement for extracellular Ca2+ in agonist-stimulated phosphoinositide turnover and its sensitivity to Ca(2+)-channel blockers, we propose a hypothetical model suggesting that Ca2+, following IP-3-mediated mobilization, exerts a facilitatory action on the activity of receptor-phospholipase C complex. We further propose that in the absence of extracellular Ca2+ or in the presence of certain Ca(2+)-channel blockers, refilling of calciosomes is ineffectual or inhibited, causing its depletion and subsequent inactivation of agonist-stimulated phosphoinositide turnover.
利用原代神经元培养物，我们研究了细胞外钙离子在受体调节的磷酸肌醇代谢中的作用。我们报告，受体（谷氨酸和乙酰胆碱）激活的磷酸肌醇代谢需要细胞外钙离子的存在（半数有效浓度 = 21.1微摩尔）。对钙离子的需求似乎在细胞内水平，并且对钙离子具有高度选择性。我们还发现，几种无机和有机钙离子通道阻滞剂，包括镧离子和维拉帕米，可抑制磷酸肌醇代谢。然而，这些药物在这方面的药理学特征与其在电压敏感性钙离子通道上的作用不同。为了解释激动剂刺激的磷酸肌醇代谢中对细胞外钙离子的上述需求及其对钙离子通道阻滞剂的敏感性，我们提出一个假设模型，表明在肌醇三磷酸介导的动员后，钙离子对受体 - 磷脂酶C复合物的活性发挥促进作用。我们进一步提出，在没有细胞外钙离子或存在某些钙离子通道阻滞剂的情况下，钙小体的再填充无效或受到抑制，导致其耗竭以及随后激动剂刺激的磷酸肌醇代谢失活。
