The overall aim of the research proposed in this application is to identify the role of central and peripheral mammalian bombesin-like (BN-like) peptides in the control of food intake. Two mammalian BN-like peptides have been identified: gastrin releasing peptide (GRP) and neuromedin B (NMB). These peptides and their corresponding receptors are differentially distributed in the gastrointestinal tract and central and peripheral nervous systems. BN-like peptides inhibit food intake following peripheral or central administration and these inhibitions appear to be mimicking actions of the endogenous peptides since both GRP and NMB receptor antagonist administration increases food intake. The proposed experiments examine the specific hypotheses that: 1) the receptor subtype mediation of peripheral and central BN-like peptides, differs; 2) the mediation of the satiety actions of peripheral BN-like peptides depends upon activation of a peripheral afferent pathway that results in a caudal hindbrain release of GRP; and 3) the central pathways mediating the satiety actions of central and peripheral BN-like peptides differ. The experiments addressing these hypotheses will employ specific antagonists and antisense oligonucleotides, c-fos immunohistochemical mapping, peripheral and central lesions and microstructural behavioral analyses. Finally, the investigators propose experiments to identify interactions between mammalian BN-like peptides and other peptides with anorexigenic actions to better understand the overall contribution of BN-like peptides in the controls of food intake. Together, the results of these experiments will significantly enhance our understanding of the actions of brain/gut peptides in food intake and body weight regulation.
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