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Cholecystokinin-Stimulated Intracellular Signal Transduction Pathways1

Dexter S. Louie

Department of Nutrition and the Center for Gastrointestinal Biology and Disease, The University of North Carolina, Chapel Hill, NC 27599-7400

Cholecystokinin stimulates a variety of physiological effects throughout the gastrointestinal tract, including exocrine pancreatic secretion, contraction of gallbladder and smooth muscle throughout the gastrointestinal tract, relaxation of the sphincter of Oddi and inhibition of gastric emptying. To initiate these responses cholecystokinin must first interact with receptors on the plasma membrane of either pancreatic acinar or smooth muscle cells. Following receptor occupation the receptor is coupled to generation of intracellular messengers, such as ions, cyclic nucleotides or derivatives of phospholipid hydrolysis. These intracellular messengers activate effectors, the systems that cause a biological response. This paper uses the exocrine pancreas as a model for cholecystokinin stimulated signal transduction and examines cholecystokinin stimulated mobilization of calcium and the activation of protein kinase C. Calcium and protein kinase C act differently to mediate either the initial or sustained phases of amylase secretion from the pancreas. The activation of protein kinase C and the rise of intracellular free calcium is necessary for the initial phase of secretion, but unimportant for the sustained phase of secretion. Calcium from extracellular sources is necessary for the sustained phase of secretion. The cholecystokinin-stimulated intracellular signaling outlined for the exocrine pancreas also occurs in other tissues for transmitting the signal from the cholecystokinin receptor to the inside of the cell.


KEY WORDS: • cholecystokinin • protein kinase C • calcium • secretion • signal transduction

1 Presented as part of the symposium "New Research in the Physiology of Cholecystokinin: Nutrition Issues" given at Experimental Biology '93 meeting, New Orleans, LA, March 28–April 1, 1993. This symposium was sponsored by the American Institute of Nutrition and the American Society for Clinical Nutrition. Guest editor for this symposium was Dexter Louie, Department of Nutrition, the University of North Carolina, Chapel Hill, NC 27599.







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