This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsuchida, T. Articles by Fujita, T. Search for Related Content PubMed PubMed Citation Articles by Tsuchida, T. Articles by Fujita, T.

Inhibition of Stimulated Amylase Secretion by Adrenomedullin in Rat Pancreatic Acini

Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo 112-8688, Japan

Address all correspondence and requests for reprints to: Dr. Hirohide Ohnishi, M.D., Ph.D., Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3–28-6 Mejirodai, Bunkyo-ku, Tokyo 112-8688, Japan. E-mail: hohnishi-tky{at}umin.ac.jp

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma and recently localized to PP cells of the pancreatic islets of Langerhans. Based on the pancreatic islet-acinar axis model, we investigated the effect of adrenomedullin on regulated exocytosis of exocrine pancreas. Using rat [¹²⁵I]adrenomedullin, specific binding sites were localized to rat pancreatic acini. We next examined the effect of adrenomedullin on 100 pM cholecystokinin (CCK)-stimulated amylase release from pancreatic acini. Adrenomedullin inhibited amylase secretion in a dose-dependent manner by approximately 50% at maximum, and the IC₅₀ was 1.1 pM. However, adrenomedullin did not affect rat [¹²⁵I]CCK binding to isolated acini or reduce the intracellular free Ca²⁺ concentration increased by CCK. Adrenomedullin also inhibited amylase secretion induced by 1 µM calcium ionophore A23187, suggesting that adrenomedullin inhibits stimulated amylase secretion by functioning at a step(s) distal to the ligand-receptor binding system and intracellular calcium mobilizing mechanism. In streptolysin-O permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve to the right, indicating that adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery. In addition, pretreatment of pancreatic acini with pertussis toxin abolished the inhibitory effect of adrenomedullin on CCK-stimulated amylase secretion. These results indicate that adrenomedullin inhibits stimulated amylase secretion by reducing the calcium sensitivity of the exocytotic machinery of the pancreatic acini. A pertussis toxin-sensitive GTP-binding protein(s) is also involved in this mechanism.

This article has been cited by other articles:

				N. Sekine, K. Takano, N. Kimata-Hayashi, T. Kadowaki, and T. Fujita Adrenomedullin inhibits insulin exocytosis via pertussis toxin-sensitive G protein-coupled mechanism. Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E9 - E14. [Abstract] [Full Text] [PDF]

				E. Bertelli and M. Bendayan Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development? J. Histochem. Cytochem., September 1, 2005; 53(9): 1071 - 1086. [Abstract] [Full Text] [PDF]

				O. Garmendia, M. P. Rodriguez, M. A. Burrell, and A. C. Villaro Immunocytochemical Finding of the Amidating Enzymes in Mouse Pancreatic A-, B-, and D-cells: A Comparison with Human and Rat J. Histochem. Cytochem., October 1, 2002; 50(10): 1401 - 1416. [Abstract] [Full Text] [PDF]

				A. Martinez, S. Kapas, M.-J. Miller, Y. Ward, and F. Cuttitta Coexpression of Receptors for Adrenomedullin, Calcitonin Gene-Related Peptide, and Amylin in Pancreatic {beta}-Cells Endocrinology, January 1, 2000; 141(1): 406 - 411. [Abstract] [Full Text] [PDF]