The effect of long-term administration of lorglumide (CR 1409) on rat pancreatic growth and enzyme composition.
The effects of lorglumide (CR 1409), a potent cholecystokinin (CCK) receptor blocker developed recently by the Rotta Research Laboratories, were studied on pancreatic growth and enzyme composition. In secretory studies, the inhibitory effect of 4 mg/kg of lorglumide administered subcutaneously proved to last more than 3 h. The trophic effect of exogenous CCK (600 ng/kg given three times daily for 2 weeks) was significantly decreased by the simultaneous administration of 4 mg/kg of lorglumide. To study the role of endogenous CCK released by feeding while maintaining pancreatic trophism, 4 mg/kg of lorglumide was administered subcutaneously four times daily during the feeding period for 2 weeks. Lorglumide significantly decreased pancreatic weight, pancreatic content of soluble protein, trypsinogen, and chymotrypsinogen, while decreases in DNA, lipase, and amylase failed to reach statistical significance. According to our experiments, high-doses of lorglumide could inhibit not only the trophic effect of exogenous CCK but also the effect of endogenous CCK released by food and lorglumide itself.
Takács
T
T
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Nagy
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I
Pap
A
A
Varró
V
V
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002919:Chymotrypsinogen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014362:Trypsinogen / Q000378:metabolism
D011506:Proteins; D014362:Trypsinogen; D004247:DNA; D002919:Chymotrypsinogen; D008049:Lipase; D000681:Amylases; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide