AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 6 1177-G1181, Copyright © 1993 by American Physiological Society

ARTICLES

Both low- and high-affinity CCK receptor states mediate trophic effects on rat pancreatic acinar cells

H. Hoshi and C. D. Logsdon
Department of Physiology, University of Michigan, Ann Arbor, Michigan 48109.

Cholecystokinin (CCK) stimulates the growth of pancreatic acinar cells. However, the molecular mechanisms involved in this trophic action are unknown. CCK binds to both high- and low-affinity receptor states, and these two states appear to activate separate sets of intracellular messengers and have opposite effects on amylase release. JMV-180 is a CCK analogue that interacts in the rat with the high-affinity state as an agonist and the low-affinity state as an antagonist. In the current study, CCK octapeptide (CCK-8) and JMV-180 were tested for their ability to stimulate the growth of rat pancreatic acinar cells in primary culture. CCK-8 stimulated [3H]thymidine incorporation into DNA in a dose-dependent manner. Effects were observed with 0.3 nM, and maximal increases were seen at 3 nM CCK-8 (442 +/- 53% of control, n = 5, P < 0.01). JMV-180 also stimulated DNA synthesis. Effects were noted with 10 nM, and a maximal increase of 267 +/- 82% (n = 4, P < 0.01) of control was stimulated by 100 nM JMV-180. These data with JMV-180 indicate that the high-affinity receptor state for CCK is capable of stimulating DNA synthesis. However, within the same experiment the effects of CCK were always significantly greater than those of JMV-180. To test whether CCK has an additional effect through interactions with the low-affinity state, the effects of a combination of JMV-180 with a maximal dose of CCK-8 were examined. JMV-180 inhibited the maximal effect of CCK-8 in a dose-dependent manner with a maximal inhibition occurring with 1 microM JMV-180. The effects of the combination of 3 nM CCK-8 and 1 microM JMV-180 were no greater than those of JMV-180 alone. Taken together these data indicate that CCK-mediated increases in DNA synthesis in rat pancreatic acinar cells in vitro occur by interactions with both high- and low-affinity receptor states.

This article has been cited by other articles:

				E. L. Holicky, E. M. Hadac, X.-Q. Ding, and L. J. Miller Molecular characterization and organ distribution of type A and B cholecystokinin receptors in cynomolgus monkey Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G507 - G514. [Abstract] [Full Text] [PDF]

				D. M. Simeone, L. Zhang, K. Graziano, B. Nicke, T. Pham, C. Schaefer, and C. D. Logsdon Smad4 mediates activation of mitogen-activated protein kinases by TGF-{beta} in pancreatic acinar cells Am J Physiol Cell Physiol, July 1, 2001; 281(1): C311 - C319. [Abstract] [Full Text] [PDF]

				L. Zhang, K. Graziano, T. Pham, C. D. Logsdon, and D. M. Simeone Adenovirus-mediated gene transfer of dominant-negative Smad4 blocks TGF-{beta} signaling in pancreatic acinar cells Am J Physiol Gastrointest Liver Physiol, June 1, 2001; 280(6): G1247 - G1253. [Abstract] [Full Text] [PDF]

				P. CORDELIER, J.-P. ESTÈVE, N. RIVARD, M. MARLETTA, N. VAYSSE, C. SUSINI, and L. BUSCAIL The activation of neuronal NO synthase is mediated by G-protein {beta}{gamma} subunit and the tyrosine phosphatase SHP-2 FASEB J, November 1, 1999; 13(14): 2037 - 2050. [Abstract] [Full Text]

				J. A. Tapia, H. A. Ferris, R. T. Jensen, and L. J. Garcia Cholecystokinin Activates PYK2/CAKbeta by a Phospholipase C-dependent Mechanism and Its Association with the Mitogen-activated Protein Kinase Signaling Pathway in Pancreatic Acinar Cells J. Biol. Chem., October 29, 1999; 274(44): 31261 - 31271. [Abstract] [Full Text] [PDF]

				B. Nicke, M.-J. Tseng, M. Fenrich, and C. D. Logsdon Adenovirus-mediated gene transfer of RasN17 inhibits specific CCK actions on pancreatic acinar cells Am J Physiol Gastrointest Liver Physiol, February 1, 1999; 276(2): G499 - G506. [Abstract] [Full Text] [PDF]

				K. Detjen, D. Yule, M.-J. Tseng, J. A. Williams, and C. D. Logsdon CCK-B receptors produce similar signals but have opposite growth effects in CHO and Swiss 3T3 cells Am J Physiol Cell Physiol, November 1, 1997; 273(5): C1449 - C1457. [Abstract] [Full Text] [PDF]

				P. Cordelier, J.-P. Esteve, C. Bousquet, N. Delesque, A.-M. O'Carroll, A. V. Schally, N. Vaysse, C. Susini, and L. Buscail Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5 PNAS, August 19, 1997; 94(17): 9343 - 9348. [Abstract] [Full Text] [PDF]