CCK satiety is differentially mediated by high- and low-affinity CCK receptors in mice and rats

S. C. Weatherford, W. B. Laughton, J. Salabarria, W. Danho, J. W. Tilley, L. A. Netterville, G. J. Schwartz, Timothy H Moran

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Abstract

Cholecystokinin-JMV-180 (JMV-180) is an analogue of cholecystokinin C- terminal octapeptide (CCK-8), which has been shown to be an agonist at the proposed CCK pancreatic high-affinity site and a functional antagonist at the pancreatic low-affinity site in rats and to have agonist activity at both high- and low-affinity sites in the mouse. In this study we used JMV-180 to evaluate the potential participation of these two CCK-A sites in the satiety effect of CCK-8 in rats and mice. When tested at doses that ranged from 0.01 to 9.2 μmol/kg, JMV-180 did not reliably affect food intake of solid or liquid test diets in rats. When combined with CCK-8 (3.2 or 8.5 nmol/kg) JMV- 180 dose dependently reversed the satiety effect of CCK-8. In contrast to these results in the rat, both JMV-180 (3.7-14.8 μmol/kg) and CCK-8 (1.7- 6.8 nmol/kg) dose dependently reduced the intake of 20% sucrose in mice. Both CCK-8- and JMV-180-induced suppression of food intake were attenuated by the CCK-A antagonist MK-329 (24.8 nmol/kg). The results of these studies suggest that agonist activity at sites pharmacologically similar to the CCK pancreatic high-affinity site is not sufficient for expression of CCK satiety, whereas agonist activity at low-affinity-like sites is necessary to reduce food intake. Thus the anorexic activity of CCK appears to be mediated through an interaction with a receptor site pharmacologically similar to the pancreatic low-affinity CCK receptor site.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume264
Issue number2 33-2
Publication statusPublished - 1993

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Keywords

  • cholecystokinin
  • cholecystokinin antagonist
  • cholecystokinin-A receptor
  • cholecystokinin-JMV-180
  • feeding
  • MK-329
  • pancreas

ASJC Scopus subject areas

  • Physiology

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