The overall goal of this proposal is to identify novel actions of mammalian bombesin (BN)-like peptides in the controls of food intake and energy balance. The mammalian BN-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been demonstrated to reduce food intake following both peripheral and central administration, but little is known about their underlying mechanisms of action. The proposed experiments examine aspects of three different hypotheses. The experiments under Specific Aim 1 will assess the idea that a GRP-ergic pathway from the hypothalamus to the caudal hindbrain plays a pivotal role in the ability of metabolic signals such as leptin to affect food intake through alterations in meal size. The experiments under Specific Aim 2 will focus on how metabolic signals indicating positive or negative energy balance alter the ability of peripheral and central GRP and NMB to inhibit food intake. Based on the demonstration that bombesin receptor subtype 3 (BRS-3) knockout mice are hyperphagic and obese, experiments under Specific Aim 3 will identify the role of this novel receptor signaling system in the control of food intake and energy balance. The experiments addressing these hypotheses will employ multiple measures of food intake and specific receptor agonists and antagonists to characterize intake and identify roles of specific receptor subpopulations, c-Fos expression as a measure of cellular activation to identify candidate brain sites where interactions occur and double-labeling techniques to characterize the phenotype of these cellular populations. Together, these studies will greatly enhance our understanding of the role of mammalian BN-like peptides in the interactions between short-term satiety signals and signals that regulate overall energy balance. Such an understanding will significantly enhance our understanding of the mechanisms underlying overall energy regulation and may lead to novel treatments for obesity or eating disorders

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (02))
Program Officer
May, Michael K
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Johns Hopkins University
Schools of Medicine
United States
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Ladenheim, Ellen E; Behles, Robert R; Bi, Sheng et al. (2009) Gastrin-releasing peptide messenger ribonucleic acid expression in the hypothalamic paraventricular nucleus is altered by melanocortin receptor stimulation and food deprivation. Endocrinology 150:672-8
Ladenheim, Ellen E; Hamilton, Nahketah L; Behles, Robert R et al. (2008) Factors contributing to obesity in bombesin receptor subtype-3-deficient mice. Endocrinology 149:971-8
Ladenheim, Ellen E; Knipp, Susan (2007) Capsaicin treatment differentially affects feeding suppression by bombesin-like peptides. Physiol Behav 91:36-41
Ladenheim, Ellen E; Emond, M; Moran, T H (2005) Leptin enhances feeding suppression and neural activation produced by systemically administered bombesin. Am J Physiol Regul Integr Comp Physiol 289:R473-R477
Hensler, J G; Ladenheim, E E; Lyons, W E (2003) Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/-) mice. J Neurochem 85:1139-47
Ladenheim, E E; Hampton, L L; Whitney, A C et al. (2002) Disruptions in feeding and body weight control in gastrin-releasing peptide receptor deficient mice. J Endocrinol 174:273-81
Moran, T H; Ladenheim, E E; Schwartz, G J (2001) Within-meal gut feedback signaling. Int J Obes Relat Metab Disord 25 Suppl 5:S39-41
Emond, M; Schwartz, G J; Ladenheim, E E et al. (1999) Central leptin modulates behavioral and neural responsivity to CCK. Am J Physiol 276:R1545-9
Ladenheim, E E; Wohn, A; White, W O et al. (1999) Inhibition of gastric emptying by bombesin-like peptides is dependent upon cholecystokinin-A receptor activation. Regul Pept 84:101-6
Ladenheim, E E; Moore, K A; Salorio, C F et al. (1997) Characterization of bombesin binding sites in the rat stomach. Eur J Pharmacol 319:245-51

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