Calmodulin in Endocrine Cells

In order to survive in a dynamic environment all living cells must be able to identify and respond to variation in specific extracellular signals. Peptide hormones comprise such signals in mammalian cells. Target cells recognize the hormone through specific receptors on the outer surface of the plasma membrane. The binding of hormone to receptor initiates a series of rapid events that eventually translates this external signal into a specific cellular response mediated by a selective alteration of the intracellular metabolism. The mechanism by which the extracellular event is transduced to an in­ tracellular event is still not totally understood. The effect of ,8-adrenergic agents on cAMP metabolism led to the proposal that cAMP was the second messenger responsible for this transduction through the activation of a cAMP-dependent protein kinase. While this mechanism explains many hormonal events, it is not compatible with the studies of Hutson et al (45) and Cherrington (13), who demonstrated that neither cAMP metabolism nor activation of cAMP-dependent protein kinase were involved in the a­ adrenergic activation of glycolysis and gluconeogenesis in rat liver. Subse­ quently Keppens et al (50) and Assimacopoulos-Jeanenett et al (3) pre­ sented data supporting the concept that the a-adrenergic response was mediated through Ca2+. Indeed calcium is intimately involved in the regula­ tion of secretion from endocrine cells. This ion enters cells by diffusion but is transported between organelles and out of the cell by an active process involving CA +_Mg2+ ATPases. Changes in the intracellular concentration of this ion leads to alterations in contractility of the cells. Such changes are due to an activation of actomyosin ATPase and controled depolymerization of the cytoplasmic microtubule network.