Inactivation of cholecystokinin octapeptide by normal and cirrhotic liver in rats.
In anesthetized rats, a marked decrease in CCK-OP activity and, to a far lesser extent, in the pancreatic secretory effect of CCK-33 were found after portal administration, compared to the femoral route. Changes in the biological activity of CCK-OP were further investigated after 30 min incubation with different subcellular liver fractions (1000 X g, 12,000 X g, microsomal fraction with or without NADPH). All the subcellular liver fractions caused an approximately 70% decrease in the CCK-effect, as calculated from dose-response relationships. The inactivation of CCK-OP after incubation with microsomal fractions of thioacetamide (TAA)-induced cirrhotic liver did not differ from that of control rats. The CCK-OP dose-response curves were similar in cirrhotic and control rats, but the pancreatic secretion was sustained to a greater extent and the inhibitory effect of supramaximal stimulation was delayed in cirrhotic rats. It was concluded that CCK-OP can be inactivated by liver proteins present in microsomal fractions, by a NADPH-independent mechanism. This inactivation did not diminish in liver cirrhosis. There were no changes in CCK-OP elimination in cirrhotic rats in vivo, thus pancreatic hypertrophy in experimental cirrhosis must be explained by other mechanisms.
Berger
Z
Z
First Department of Medicine, University Medical School, Szeged, Hungary.
Pap
A
A
Ungi
I
I
Varró
V
V
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D005260:Female; D005268:Femoral Vein; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008099:Liver / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D011169:Portal Vein; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D014357:Trypsin / Q000378:metabolism
D010446:Peptide Fragments; D011506:Proteins; C049614:cholecystokinin 33 (10-20); D002766:Cholecystokinin; D014357:Trypsin; D012844:Sincalide