NEUROPEPTIDE Y2 RECEPTORS ON NERVE-ENDINGS FROM THE RAT NEUROHYPOPHYSIS REGULATE VASOPRESSIN AND OXYTOCIN RELEASE

Neuropeptide Y and peptide YY are important central and peripheral mod ulators of cardiovascular and neuroendocrine functions, that act throu gh multiple receptor subtypes, Y1 through Y5. A neuropeptide Y-binding site of the Y2 type was characterized by ligand binding studies in is olated nerve terminals from the rat neurohypophysis. Functionally, neu ropeptide Y and peptide YY dose-dependently triggered arginine 8-vasop ressin and oxytocin release from perfused isolated terminals, and pote ntiated the arginine-8-vasopressin release induced by depolarization. Osmotic stimulation by salt loading of rats for two and seven days cau sed a more than three-fold increase in the neuropeptide Y content of t he nerve endings. However, the Y2 receptor expression and arginine-8-v asopressin content declined, showing that the neuropeptide Y system is dynamic and suggesting that it plays a physiological role in salt and water homeostasis. Two sets of observations suggest the arginine-8-va sopressin release by neuropeptide Y may not be explained by neuropepti de Y effects on intracellular Ca2+. First, absence of Ca2+ from the pe rfusion medium did not affect the arginine 8-vasopressin release, and secondly neuropeptide Y did not change intraterminal Ca2+ concentratio ns. Pretreatment with pertussis toxin blocked arginine-8-vasopressin s ecretion by neuropeptide Y, suggesting activation of G(i) or G(o) hete rotrimeric G-proteins are required for secretion. It is concluded, tha t the nerve endings of the neurohypophysis contain a complete neuropep tide Y system with ligand and receptors. Neuropeptide Y may act in an autocrine fashion via activation of Y2 neuropeptide Y receptors to sti mulate the release of vasopressin and oxytocin via a G(i)/G(o) depende nt secretory mechanism.