A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats

Pancreas. 1994 Mar;9(2):225-9. doi: 10.1097/00006676-199403000-00013.

Abstract

We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caseins / pharmacology
  • Cholecystokinin / pharmacology
  • Duodenum
  • Male
  • Molecular Structure
  • Naphthalenes / administration & dosage*
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pentanoic Acids / administration & dosage*
  • Rats
  • Rats, Wistar
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin / antagonists & inhibitors*

Substances

  • Caseins
  • Naphthalenes
  • Pentanoic Acids
  • Receptor, Cholecystokinin A
  • Receptors, Cholecystokinin
  • KSG 504
  • Cholecystokinin