Stimulation of in vivo pancreatic growth in the rat is mediated specifically by way of cholecystokinin-A receptors.
OBJECTIVE
Cholecystokinin (CCK) and gastrin stimulate growth of rodent pancreas in vivo. However, it remains unclear whether these growth effects are mediated specifically by CCK-A receptors, CCK-B receptors, or both. To clarify this issue, the present study examined the effect of highly selective and biologically active CCK agonists on pancreatic growth.


METHODS
Rats were subcutaneously injected with either (1) CCK-8, a nonselective CCK agonist (2.50 micrograms/kg body wt); (2) A-71623, a selective CCK-A agonist, tert-butyl-oxycarbonyl-Trp-Lys (epsilon-N-2-methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 (1.84 micrograms/kg body wt); (3) SNF-8815; a selective CCK-B agonist, [(2R,3S)-beta-MePhe28, N-MeNle31]CCK26-33 (2.40 micrograms/kg body wt); or (4) saline (control) for 21 days. Rats were killed, and pancreatic weight, protein content, RNA content, DNA content, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells were determined.


RESULTS
Nonselective CCK agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, and number of mitoses per 10,000 acinar cells. Likewise, selective CCK-A agonist significantly increased pancreatic weight, protein, RNA, and DNA contents, protein-DNA ratio, RNA-DNA ratio, pancreatic area per nucleus, and number of mitoses per 10,000 acinar cells. In contrast, selective and biologically active CCK-B agonist had no effect.


CONCLUSIONS
These findings indicate that pancreatic growth is mediated specifically by CCK-A receptors in the rat in vivo.
Povoski
S P
SP
Department of Surgery, University of Cincinnati College of Medicine, Ohio.
Zhou
W
W
Longnecker
D S
DS
Jensen
R T
RT
Mantey
S A
SA
Bell
R H
RH
D000818:Animals; D001667:Binding, Competitive; D002766:Cholecystokinin / Q000819:agonists / Q000031:analogs & derivatives / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology; D008297:Male; D008938:Mitosis; D010179:Pancreas / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D005755:Gastrins; D010446:Peptide Fragments; D011506:Proteins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C066278:A 71623; C082766:SNF 8815; C013550:gastrin 17; D012313:RNA; D004247:DNA; D002766:Cholecystokinin