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

• Published in: Advances in physiology education 2009-09, Vol.33 (3), p.175-186
• Main Author: Misler, Stanley
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Catecholamines - secretion; Cells; Cytology; Diabetes; Diseases; Endocrine Cells - secretion; Endocrine system; Exocytosis; Fluorescence; Humans; Molecular Structure; Physiology; Science Instruction; Scientific Research; Staying Current; Teaching Methods
• ISSN: 1043-4046; 1522-1229
• DOI: 10.1152/advan.90213.2008

Department of Internal Medicine and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri Address for reprint requests and other correspondence: S. Misler, Dept. of Internal Medicine and Dept. of Cell Biology and Physiology, Washington Univ. School of Medicine, Box 8126, St. Louis, MO 63110 (e-mail: smisler{at}dom.wustl.edu ). Abstract Stimulus-secretion 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 2+ entry-dependent SSC (characteristic of neurons) with G protein receptor-coupled, Ca 2+ release-dependent, 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 2+ 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 2+ -sensitive parathyroid chief cells secreting parathyroid hormone, and glucose-sensitive β- 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 2+ sensitivity, resulting in the hyperparathyroidism of renal disease, and defects in biphasic insulin secretion, resulting in diabetes mellitus. Key words: ion channels; exocytosis; granule pools; adrenal chromaffin cells; neuroendocrine cells; pancreatic islet β- and -cells