Role of bombesin-related peptides in the mediation or integration of the stress response

Abstract

In addition to the relatively well established role of corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in the mediation of the stress response, there is reason to believe that bombesin-like peptides (BN-LPs) may also contribute to the mediation or integration of these responses and thus might be considered as putative 'stress peptides'. This review provides evidence supporting this contention by showing that (i) BN-LPs are present at brain sites known to be activated by stressors, (ii) stressor exposure alters utilization of BN-related peptides, (iii) exogenous BN administration mimics the endocrine, autonomic and/or behavioral effects elicited by stressors, and (iv) antagonism of BN action attenuates the behavioral and/or neurochemical effects of stressors or of exogenously administered peptide. The evidence presented also suggests that BN-LPs mediate their stress-relevant effects through activation of CRH and/or AVP neurons. Several hypothetical mechanisms for such peptidergic interactions are discussed as to the implications of considering BN-LPs as 'stress peptides'.

Bombesin Receptors as a Novel Anti-Anxiety Therapeutic Target: BB1Receptor Actions on Anxiety through Alterations of Serotonin Activity

“…Although the developmental mecha- nisms leading to the recruitment of various peptidergic systems in the mediation of diverse behaviors is not well understood (Fink et al, 1998;Strand, 1999), in the context of danger signals, suppression of nondefensive (e.g., feeding) behaviors would be a highly adaptive response, and hence overlapping or interacting neural circuits for appetitively and aversively motivated behaviors might be expected. The present study hinges on the working hypothesis that mammalian BB-peptides that had been implicated in satiety processes, namely GRP and NMB, may also contribute to the integration and/or mediation of stress/anxiety responses (Merali et al, 2002). Indeed, it seems that many aversive and appetitive events activate some of the same neuronal circuits (Merali et al, 1998.…”

“…Although the BB peptide family was initially implicated in the mediation of peripheral satiety signals (Gibbs et al, 1979;Kulkosky et al, 1982;Merali et al, 1999), more recent studies suggested that these peptides may be active neuromodulators/neuromediators affecting several brain mechanisms and altering behaviors associated with stress and anxiety (Merali et al, 1998(Merali et al, , 2002. The phylogenetic conservation of so-called "gut-brain" peptides (e.g., CCK and BB-like peptides) suggests their importance from an evolutionary perspective.…”

Anticipatory Cues Differentially Provoke In Vivo Peptidergic and Monoaminergic Release at the Medial Prefrontal Cortex

“…Likewise, while CRH within the amygdala has been implicated in appetitive as well as aversive processes , it is uncertain whether changes of CRH are provoked in the mPFC in response to appetitive stimuli or cues that predict reward. Finally, GRP, which acts as a satiety peptide, has been shown to vary in response to food ingestion (Merali et al, 2002), but again, little is known about the GRP response to anticipatory stimuli. The present investigation assessed the influence of ingestion and anticipatory stimuli on neurochemical functioning within the mPFC, specifically whether such effects were unique to particular transmitters (eg variations of GRP, as a satiety peptide, would be aligned with ingestive processes, while DA and 5-HT changes would be evident in response to anticipatory cues).…”

“…Although the satiety effects of GRP (and related peptides, for example, bombesin) have been extensively assessed (Babcock et al, 1985;Gibbs, 1985;Gibbs et al, 1979;Gibbs and Smith, 1988;Merali et al, 1999Merali et al, , 2002, there is a paucity of information concerning the involvement of this peptide in relation to reward or anticipatory mechanisms. In the current investigation, the Cue Relevant and Extinction groups displayed comparable increases of GRP in response to the anticipatory cues; but, in the Cue Relevant group, this increase was most pronounced once rats engaged in actual food ingestion.…”

“…It would be of considerable interest to determine whether this peptide is also involved in anticipatory processes. Furthermore, gastrin-releasing peptide (GRP), which is activated with food ingestion and stimulates hypothalamic-pituitary-adrenal activity (Gibbs et al, 1979;Gibbs and Smith, 1988;Kent et al, 1998;Merali et al, 1999Merali et al, , 2002, is released at the central amygdala in response to both appetitive and aversive stimuli . Although CRH and GRP systems may functionally be interlinked (Merali et al, 2002), and receptors for both peptides are expressed within the mPFC (Kroog et al, 1995;Radulovic et al, 1998), limited information is available as to whether these peptides are associated with anticipatory processes.…”