Physiological role of bombesin-like peptides in the regulation of food intake: Ontogenic profile and mechanisms of action.

Abstract

This research aimed to characterize the physiological role of bombesin-like peptides (BN-LP) in the control of ingestion. The first experiment assessed the developmental profile of BN response in rats, and demonstrated that BN effectively suppressed feeding from postnatal day (PD) 1 through PD 15. Pretreatment with BN receptor antagonist blocked this suppression, suggesting that BN receptors are functional and may participate in feeding regulation from the first hours following birth. We then examined whether endogenous levels of BN-LP in the brain changed in a meal-dependent manner. Of the 15 distinct nuclei examined, meal-related alterations in BN-LP were observed at the hypothalamic paraventricular (PVN), arcuate and dorsomedial nuclei and at the nucleus accumbens. These alterations appeared site and peptide specific since changes in CRF levels were restricted to the hypothalamic lateral and ventromedial nuclei and the central nucleus of the amygdala. To determine what these changes meant in terms of peptide utilization, we then monitored the in vivo release of BN-LP as compared to the preprandial and/or postprandial conditions, where the interstitial levels of BN-LP were relatively high. The next study examined whether sustained central exposure to a BN agonist affected spontaneous feeding, ingestive response to acute BN, or the density of BN receptors within the CNS. Feeding was suppressed over the initial 48 h of BN infusion, however, tolerance to this effect was apparent by 72 h and was associated with receptor down-regulation at the PVN and dentate gyrus. Acute BN administration suppressed feeding in both the chronic BN exposed and control groups indicating lack of tolerance to the acute fluctuations of BN. These findings imply the existence of different neural mechanism(s) mediating the acute versus long-term effects of BN. Finally, the potential interactions of BN with other satiety peptides were investigated. These studies revealed that BN partly mediates its satiety effects through interactions with CRF. The specificity of this interaction was supported by the lack of interaction between BN and/or CRF with oxytocin. This series of experiments provide novel data supporting the view that BN-LP play an important role in the regulation of food intake, and provide some new insights into their possible mechanism(s) of action.