Calcium Antagonists and Hormone Release

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.