Calcium antagonists and hormone release.
Calcium antagonists and hormone release.
复制标题
钙拮抗剂和激素释放。
作者：
J. Millar;A. Struthers
简介：钙（Ca2+）被恰当地称为“万能的调节器”[1]，以表彰其许多不可或缺的代谢作用。这类药物通常被称为钙拮抗剂（钙慢通道阻滞剂），引起各种药理学作用，这些药物可用作钙依赖机制的探针。这种应用似乎特别合适的一个领域是激素释放的研究，因为已经证明至少一些激素的分泌依赖于细胞外Ca 2+跨细胞膜的转运。此外，对大多数激素分泌的特定生理刺激可以在体内应用或在体外模拟，并且激素水平可以通过特定测定来测量。钙拮抗剂也提供了一种可能的手段，研究在完整的有机体中的激素释放的Ca 2+的作用。在许多研究中，钙拮抗剂对分泌刺激的激素反应的抑制作用已被视为Ca2+跨膜通量是反应中的强制性事件的证据。这样的结论引出了几个问题，这些问题将在本次审查中讨论。例如，重要的是要确定钙拮抗剂在多大程度上代表了同类药物，“拮抗作用”是否仅限于抑制内向钙流，以及药理作用是否根据所用药物或所研究的细胞类型而变化。回答这些问题是必要的，以排除钙拮抗剂的作用，而不是防止钙吸收，可能会抑制激素释放。
Introduction: Calcium (Ca2+) has been aptly entitled the ‘universal provocateur’ [1] in recognition of its many indispensable metabolic actions. The class of drugs popularly known as calcium antagonists (calcium slow channel blockers) provokes a variety of pharmacological effects and these drugs are useful as probes of calcium-dependent mechanisms. One area where such application appears particularly appropriate is the study of hormone release, since it has been demonstrated that secretion of at least some hormones is dependent on translocation of extracellular Ca2+ across the cell membrane. Furthermore, specific physiological stimuli to secretion of most hormones can be applied in vivo or mimicked in vitro, and hormone levels may be measured by specific assays. Calcium antagonists also provide a possible means of studying the role of Ca2+ in hormone release in the intact organism. In many studies an inhibitory effect of a calcium antagonist on hormonal responses to secretory stimuli has been taken as evidence that transmembrane flux of Ca2+ is an obligatory event in the response. Such a conclusion begs several questions, which will be discussed in this review. For example, it is important to define the extent to which calcium antagonists represent a homogeneous class of drugs, whether ‘antagonism’ is restricted to inhibition of inward calcium flux, and whether the pharmacological actions vary according to the agent used or the cell type under study. Answers to such questions are necessary to exclude actions of calcium antagonists other than prevention of calcium uptake which may inhibit hormone release.