Staying Current Unifying concepts in stimulus-secretion coupling in endocrine cells and some implications for therapeutics

Misler S. Unifying concepts in stimulus-secretion coupling in endocrine cells and some implications for therapeutics. Adv Physiol Educ 33: 175–186, 2009; doi:10.1152/advan.90213.2008.—Stimulussecretion coupling (SSC) in endocrine cells remains underappreciated as a subject for the study/teaching of general physiology. In the present article, we review key new electrophysiological, electrochemical, and fluorescence optical techniques for the study of exocytosis in single cells that have made this a fertile area for recent research. Based on findings using these techniques, we developed a model of SSC for adrenal chromaffin cells that blends features of Ca entry-dependent SSC (characteristic of neurons) with G protein receptor-coupled, Ca releasedependent, and second messenger-dependent SSC (characteristic of epithelial exocrine cells and nucleated blood cells). This model requires two distinct pools of secretory graunules with differing Ca sensitivities. We extended this model to account for SSC in a wide variety of peripheral and hypothalamic/pituitary-based endocrine cells. These include osmosensitive magnocellular neurosecretory cells releasing antidiuretic hormone, stretch-sensitive atrial myocytes secreting atrial natriuretic peptide, K -sensitive adrenal glomerulosa cells secreting aldosterone, Ca -sensitive parathyroid chief cells secreting parathyroid hormone, and glucose-sensitive and -cells of pancreatic islets secreting insulin and glucagon, respectively. We conclude this article with implications of this approach for pathophysiology and therapeutics, including defects in chief cell Ca sensitivity, resulting in the hyperparathyroidism of renal disease, and defects in biphasic insulin secretion, resulting in diabetes mellitus.