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, T. H. Moran

Research output: Contribution to journalArticle

51 Scopus citations

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)
Pages (from-to)R244-R249
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume264
Issue number2 33-2
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Weatherford, S. C., Laughton, W. B., Salabarria, J., Danho, W., Tilley, J. W., Netterville, L. A., Schwartz, G. J., & Moran, T. H. (1993). CCK satiety is differentially mediated by high- and low-affinity CCK receptors in mice and rats. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 264(2 33-2), R244-R249.