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Am J Physiol Gastrointest Liver Physiol 288: G866-G879, 2005. First published November 18, 2004; doi:10.1152/ajpgi.00389.2003
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HORMONES AND SIGNALING

Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8

M. Yamamoto,1 J. R. Reeve, Jr.,2 D. A. Keire,2 and G. M. Green1

1Department of Physiology, University of Texas Health Science Center, San Antonio, Texas; 2Center for Ulcer Research and Education: Digestive Diseases Research Center, Department of Veterans Affairs Greater Los Angeles Healthcare System, and Digestive Diseases Division, University of California, Los Angeles School of Medicine, Los Angeles, California

Submitted 8 September 2003 ; accepted in final form 3 November 2004

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.

cholecystokinin; secretin; electrolyte secretion; bicarbonate secretion; chloride secretion



Address for reprint requests and other correspondence: J. R. Reeve, Jr., CURE: Digestive Disease Research Center, Dept. of Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073 (E-mail: jreeve{at}ucla.edu)




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