Vasopressin Neuromodulation in Neuroendocrine Hypothalamus: Receptors, Signal Transduction and Physiological Significance

University Of California-Riverside, Riverside CA

Investigators

Abstract

Vasopressin Neuromodulation in Neuroendocrine Hypothalamus: Receptors, Signal Transduction and Physiological Significance Neuroendocrine cells (MNCs) located in the supraoptic nucleus (SON) of the brain release the peptides oxytocin (OXY) and vasopressin (VP) that are critical for hydromineral balance, lactation, the birth process and cardiovascular function. VP and OXY get liberated into the bloodstream and target the kidneys, uterus, arteries and mammary glands. Local release of VP and OXY allow MNCs to participate in their autoregulation. It has been previously determined that treatment of SON tissue from adult rats with VP and OXY can decrease the release of the stimulatory chemical glutamate (GLU) that mediates the transfer of information from other brain regions to the SON. During activated states such as dehydration and lactation these signals provoke the release of VP and OXY from MNCs and hence the modulatory roles of these peptides on incoming signals becomes critical. In concert with other effects of local peptide release, this level of control may prevent depletion of hormone supply during periods of prolonged activation and help maintain the efficiency of MNC controlled osmoregulatory and other homeostatic systems that sustain life in land and aquatic vertebrates. The components of this circuit are unknown and the proposed experiments will characterize the receptor subtypes and potential downstream signal transduction cascades involved in VP's actions on GLU release. Levels of GLU and VP in the SON will be correlated in perfusates from SON punches using HPLC and enzyme immunoassay. Other experiments will investigate the source of GLU release and VP's modulatory actions. The physiological significance of the dramatic and potentially important effect of local VP on glutamatergic transmission in rats subjected to dehydration will also be examined. Commensurate with the PI's strong commitment to the development of young scientists, the proposed studies will involve the training of undergraduate, graduate and postdoctoral scientists.