Comparison of hepatic elimination of different forms of cholecystokinin in dogs. Bioassay and radioimmunoassay comparisons of cholecystokinin-8-sulfate and -33-sulfate.

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Abstract

The influence of hepatic transit on the ability of exogenous cholecystokinin-8-sulfate and -33-sulfate (CCK-8 and CCK-33, respectively) to stimulate gallbladder contraction and exocrine pancreatic secretion, as well as on the peripheral plasma concentration of each agent, was evaluated in five conscious dogs with pancreatic and gallbladder fistulas and complete portacaval transposition. The gallbladder pressure increments after portal administration of CCK-8 (0.125, 0.25, 0.50, and 1.0 microgram/kg per h for 5 min) were diminished by 36, 45, 39 and 25%, respectively, in comparison with those obtained with systemic administration of identical doses of CCK-8 (P less than 0.05). In a subsequent experiment, the integrated pancreatic juice volume, bicarbonate, and protein secretion were diminished by 22, 32, and 48%, respectively, during a 30-min infusion of CCK-8 (0.10 micrograms/kg per h) into the portal venous system, in comparison with the results obtained with systemic administration of CCK-8 (P less than 0.05). In contrast, the gallbladder pressure and pancreatic exocrine secretory responses to portal administration of CCK-33 did not differ significantly (P greater than 0.05) from the results obtained with systemic administration of CCK-33. Radioimmunoassay for CCK-8 in plasma showed that the integrated CCK-8 value during portal administration was significantly lower (P less than 0.05) than it was during systemic administration. The results for CCK-33, however, did not vary, whether it was given by a systemic or portal route (P greater than 0.05). Thus, the present study demonstrates that CCK-8 is partially inactivated by the liver whereas CCK-33 is not, which suggests that CCK-3 in the circulation may play a significant role in the physiologic regulation of the gallbladder and exocrine pancreas.

Authors

T Sakamoto, M Fujimura, J Newman, X G Zhu, G H Greeley Jr, J C Thompson