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Am J Physiol Gastrointest Liver Physiol (November 6, 2003). doi:10.1152/ajpgi.00020.2003
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Submitted on January 15, 2003
Accepted on September 17, 2003

Differential bile-pancreatic secretory effects of CCK-58 and CCK-8

Joseph R. Reeve, Jr.1*, S. Vincent Wu1, David A. Keire1, Kym Faull2, Peter Chew1, Travis E. Solomon1, Gary M. Green3, and Tamer Coskun1

1 CURE: Digestive Diseases Research Center, VA GLAHS, Los Angeles, CA, USA; Digestive Diseases Division, UCLA School of Medicine, Los Angeles, CA, USA
2 Pasarow Mass Spectrometry Laboratory, Departments of Psychiatry & Biobehavioral Sciences and the Neuropsychiatric Institute, and Chemistry & Biochemistry, UCLA, Los Angeles, CA, USA
3 Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

* To whom correspondence should be addressed. E-mail: jreeve{at}ucla.edu.

In this work we 1) synthesize rat CCK-58, 2) determine the amounts and forms of rat cholecystokinin in whole blood after stimulation of its release by casein, 3) determine the potency of CCK-8 and CCK-58 peptides to displace labeled CCK-8 from CCK-A and CCK-B receptors transfected into CHO cells, and 4) examine the biological actions of CCK-8 and rat CCK-58 in an anesthetized rat model. CCK-58 was the only detected endocrine form of cholecystokinin in rat blood. Synthetic rat CCK-58 was less potent that CCK-8 for displacing label from CCK-A and CCK-B receptors in transfected CHO cells. However, rat CCK-58 was more potent than CCK-8 for stimulation of pancreatic protein secretion in the anesthetized rat. In addition, CCK-58, but not CCK-8 stimulated fluid secretion in this anesthetized rat model. These data suggest that regions outside the C-terminus of rat CCK-58 influence the expression of cholecystokinin biological activity. The presence of only CCK-58 in the circulation and the fact that its biological activity differs from CCK-8 suggests that CCK-58 deserves scrutiny in other physiological models of cholecystokinin activity.




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