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

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

Hisakazu Hoshi and Craig D Logsdon
The American journal of physiology, Vol.265(6 Pt 1), pp.G1177-G1181
12/1993
DOI: 10.1152/ajpgi.1993.265.6.G1177
PMID: 8279569

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Abstract

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.
 Pancreas - cytology Cells, Cultured Sincalide - analogs & derivatives Sincalide - pharmacology Pancreas - drug effects Rats Tritium Cell Division - drug effects Dose-Response Relationship, Drug Receptors, Cholecystokinin - drug effects Receptors, Cholecystokinin - physiology Animals Time Factors DNA - biosynthesis Pancreas - physiology Kinetics Thymidine - metabolism

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