Peptidergic mediation of response to stress: Focus on bombesin-like peptides.

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 the bombesin (BN) family of peptides may also contribute to the integration of these responses. Indeed, central administration of BN-like peptides produces endocrine, autonomic and behavioral effects, resembling those elicited by stressor exposure as well as by exogenously administered CRH and/or AVP. These observations led us to hypothesize that BN-like peptides may be important mediators of the stress response and that this family of peptides may mediate their stress-relevant effects via activation of CRH and/or AVP circuits. Using physiological approaches we demonstrated that stressor exposure is associated with changes in post-mortem tissue levels of BN-like peptides, BN-like peptide receptor densities and in the in vivo release of BN-like peptides from selected brain sites. Using pharmacological approaches we showed that (1) blockade of central CRH receptors with alphah-CRF attenuated BN-induced neuroendocrine and autonomic activation and (2) central BN administration elicited site-specific alterations in endogenous levels of CRH and AVP as well as the release of CRH and AVP from selected brain sites. Together, these data provide evidence for the involvement of BN-like peptides in the mediation and/or modulation of the stress response via activation of CRH and/or AVP neurons