The long-range goal of this project is to understand the roles of endogenous mammalian bombesin-like peptides -- gastrin releasing peptide (GRP) and neuromedin B (NMB) -- in the peripheral generation and central neural processing of the physiological signals that limit meal size and regulate the length of the intermeal interval in rats. Despite accumulating evidence that endogenous GRP and NMB are important for both functions in animals and humans, two critical problems remain unsolved: the initial site of action for each peptide, and whether either is physiologically relevant to the normal meal pattern. Results obtained by these investigators demonstrate that peripherally administered bombesin acts in the upper abdomen, within the bed of the coeliac artery. They propose that endogenous GRP and/or NMB act initially in the stomach, making an important physiological contribution to the normal meal pattern. To establish a normal meal pattern, the investigators will employ a spontaneously feeding, undisturbed rat preparation. To track sequential meals and intermeal intervals, and to permit the microstructural analysis of individual meals, they will record second-by-second intakes of liquid food using lickometers. To locate the sites of action, they will deliver GRP and NMB by close arterial infusion to organ-selective sites in the upper abdomen. To determine the physiological relevance of GRP and NMB, they will employ potent, highly-selective receptor antagonists for each peptide. This research will provide a decisive test of the hypothesis at risk: Endogenous GRP and NMB, released from intrinsic nerves in the stomach wall, act locally to limit meal size and regulate intermeal interval length under spontaneous feeding conditions. Successful resolution of this primary issue will establish the base required to understand the specific neural and humoral events that relay these peptide-initiated satiety signals centrally, and their anatomical sites of entry into brain tissue.
| 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 |
