Characterization of noradrenergic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system.

Evidence is presented indicating that norepinephrine (NE) inhibits vasopressin (VP) release from the rat hypothalamo-neurohypophyseal explant under some, but not all, conditions in vitro. NE at 10(-5) M inhibited basal VP release and inhibited acetylcholine-induced release in a concentration-dependent fashion. However, the induction of VP release caused by the addition of NaCl (sufficient to yield a 10 mosmol/kg H2O increase in culture medium osmolality) was not reduced by NE in concentrations as high as 10(-5) M. An alpha-adrenergic receptor mediation of the inhibition of VP release by NE was suggested by the ability of phentolamine and phenoxybenzamine, but not propranolol, to block this effect. In addition, phentolamine at 10(-4) M, but not equimolar amounts of propranolol, increased VP release when added alone on day 2 of culture, but not on days 3 or 4. Histofluorescence examination of additional explants revealed that endogenous catecholamine was still present on day 2 within varicosities in the supraoptic nucleus, but diminished by days 3 and 4, suggesting that endogenous NE could influence basal VP release. The results indicate that NE can inhibit spontaneous and cholinergically stimulated VP release from the hypothalamo-neurohypophyseal explant, but osmotic stimulation renders the explants insensitive to attenuation of VP release by NE.