Role of cholecystokinin in cholestyramine-induced changes of the exocrine pancreas.
This study was an investigation of the role of cholecystokinin (CCK) in the stimulatory action of cholestyramine on rat exocrine pancreas. Postprandial CCK release was significantly enhanced by acute administration of cholestyramine (12.7 +/- 1.8 vs 3.7 +/- 0.5 pmol/L in controls). Over four weeks, rats were fed either regular diet or diet containing 6% cholestyramine, and were treated with the specific CCK receptor antagonist L-364,718 (2 x 0.5 mg/kg body weight/day s.c.) or DMSO (vehicle for the antagonist). Cholestyramine significantly increased pancreatic weight and trypsin and chymotrypsin contents. L-364,718 abolished these effects. Concomitant administration of antagonist and cholestyramine elevated amylase content, compared to controls. CCK levels in fasted animals did not differ between the four groups. The effect of the same dose of L-364,718 on pancreatic enzyme depletion, induced by the protease inhibitor camostate, was studied in a control experiment. A single dose of camostate (200 mg/kg) caused a 44-68% decrease in enzyme content. L-364,718 reversed this effect for all enzymes. We conclude that CCK is the mediator of cholestyramine-induced pancreatic hypertrophy and increase in content of proteases. After long-term administration, the CCK receptor antagonist, in combination with cholestyramine revealed an agonistic effect on individual, pancreatic enzyme content.
Koop
I
I
Department of Internal Medicine, University of Marburg, F.R.G.
Lindenthal
M
M
Schade
M
M
Trautmann
M
M
Adler
G
G
Arnold
R
R
D000284:Administration, Oral; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000494:pharmacology*; D002918:Chymotrypsin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020109:Devazepide; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000009:adverse effects / Q000494:pharmacology; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000009:adverse effects / Q000494:pharmacology
D001570:Benzodiazepinones; D004952:Esters; D006146:Guanidines; D011949:Receptors, Cholecystokinin; D014361:Trypsin Inhibitors; C034532:camostat; D002792:Cholestyramine Resin; D016670:Gabexate; D004247:DNA; D002766:Cholecystokinin; D002918:Chymotrypsin; D014357:Trypsin; D020109:Devazepide; D004121:Dimethyl Sulfoxide