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.
First Department of Medicine, Albert Szent-Györgyi Medical University, Szeged, Hungary.
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Takács
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Nagy
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Varró
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