Central regulation of stress responses: regulation of the autonomic nervous system and visceral function by corticotrophin releasing factor-41.

Our understanding of the role of CRF in mediating integrated endocrine, autonomic and visceral stress responses is rudimentary at best. Delineating the large number of neurochemical factors that influence the activity of CRF-containing hypophyseotrophic neurones offers one direction for future research in this area. Another approach might be to examine the neuropharmacological actions of transmitters which are co-localized within CRF-containing neurones. For example, CRF and dynorphin-related peptides coexist within a subpopulation of paraventricular neurones (Roth et al, 1983), suggesting the potential for their simultaneous release and possible functional interactions between them. Interestingly, CRF and dynorphin-related peptides exhibit reciprocal actions on the release of each other in vitro and in vivo. CRF stimulates the release of immunoreactive dynorphin from rat hypothalamic slices (Nikolarakis et al, 1986) while dynorphin A1-17 inhibits the basal secretion of immunoreactive CRF from rat hypothalami (Yajima et al, 1986). In vivo experiments demonstrate that i.c.v. administration of dynorphin A1-13 reduces basal and hypotension-induced secretion of CRF into hypophyseal portal blood (Plotsky, 1986). Recent studies suggest that, in addition to their interactions at the level of release, these peptides may also modify the CNS actions of each other on autonomic and cardiovascular function (Overton and Fisher, 1989b). Thus, CRF-induced elevations of arterial pressure, heart rate and plasma catecholamine levels are attenuated by co-administration of low doses of dynorphin A1-17. The reciprocal release actions and neuropharmacological interactions between CRF and dynorphin A1-17 suggest that local integration or perhaps feedback regulation of stress-induced autonomic and cardiovascular responses may be achieved by the co-release of multiple neurotransmitters from a single source. In summary, the combined anatomical, pharmacological and physiological data provide support for the involvement of CRF neuronal systems in mediating the integration of endocrine, autonomic, and visceral functions, particularly in response to stress. Future research in this area may contribute to our understanding of the neurobiology of CRF as well as the CNS mechanisms governing homeostasis.