CCK satiety is differentially mediated by high- and low-affinity CCK receptors in mice and rats
| Autor: | W. Danho, George J. Schwartz, L. A. Netterville, W. B. Laughton, S. C. Weatherford, Timothy H. Moran, J. W. Tilley, J. Salabarria |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Agonist Sucrose medicine.medical_specialty Physiology medicine.drug_class Devazepide Biology Satiety Response digestive system Cholecystokinin receptor Sincalide Rats Sprague-Dawley Eating Mice Cholecystokinin antagonist Physiology (medical) Internal medicine medicine Animals Cholecystokinin A receptor Cholecystokinin Benzodiazepinones Mice Inbred ICR Dose-Response Relationship Drug digestive oral and skin physiology Antagonist Rats Glucose Endocrinology Receptors Cholecystokinin hormones hormone substitutes and hormone antagonists |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 264:R244-R249 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.1993.264.2.r244 |
| Popis: | 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 mumol/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 mumol/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. |
| Databáze: | OpenAIRE |
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