The long-term goal of this project is to understand the roles of endogenous mammalian bombesin-like peptides in the peripheral generation and in the central neural processing of the physiological satiety signals which serve to limit meal size and to regulate the length of the postprandial intermeal interval in rats. Recent results indicate (1) that the site of the satiety action of peripherally-administered bombesin is located in the upper abdomen, probably in intrinsic nerves of the stomach, (2) that afferent vagal and spinal-visceral nerves relay bombesin-initiated satiety signals centrally, (3) that endogenous bombesin-like peptides of the hindbrain play a key role in the central processing of satiety signals, and (4) that serotonin systems are required for the expression of bombesin-induced satiety. Focussing on these four issues, and using newly-developed surgical techniques, chemical ablations, and selective antagonists, we will determine: (1) the specific site of action of peripherally-administered bombesin-like peptides within stomach, and whether endogenous bombesin-like peptides at that site are necessary for normal satiety; (2) the specific spinal-visceral pathways mediating bombesin-induced satiety; (3) the receptive field in dorsal hindbrain for satiety signals generated by peripherally-administered bombesin-like peptides, and the role of endogenous bombesin-like peptides at that site; and (4) the locus and serotonin receptor subtype(s) mediating interactions between bombesin-like peptide systems and serotonin systems in satiety. If the bombesin family of peptides is shown to function as a physiological mediator of postprandial satiety at peripheral and central sites, this finding will have fundamental implications for the analysis of normal feeding behavior and for the determination of the pathophysiology and treatment of the two major satiety disorders in humans, bulimia nervosa and obesity.
| Overduin, Joost; Gibbs, James; Cummings, David E et al. (2014) CCK-58 elicits both satiety and satiation in rats while CCK-8 elicits only satiation. Peptides 54:71-80 |
| Kirkham, T C; Walsh, C A; Gibbs, J et al. (1994) A novel bombesin receptor antagonist selectively blocks the satiety action of peripherally administered bombesin. Pharmacol Biochem Behav 48:809-11 |
