Osmoregulation of vasopressin secretion via activation of neurohypophysialnerve terminals glycine receptors by glial taurine

Osmotic regulation of supraoptic nucleus (SON) neuron activity depends in p art on activation of neuronal glycine receptors (GlyRs), most probably by t aurine released from adjacent astrocytes. In the neurohypophysis in which t he axons of SON neurons terminate, taurine is also concentrated in and osmo -dependently released by pituicytes, the specialized glial cells ensheathin g nerve terminals. We now show that taurine release from isolated neurohypo physes is enhanced by hypo-osmotic and decreased by hyper-osmotic stimulati on. The high osmo-sensitivity is shown by the significant increase on only 3.3% reduction in osmolarity. inhibition of taurine release by 5-nitro-2-(3 -phenylpropylamino)benzoic acid, niflumic acid, and 4,4 ' -diisothlocyanato stilbene-2,2 ' -disulfonic acid suggests the involvement of volume-sensitiv e anion channels. On purified neurohypophysial nerve endings, activation of strychnine-sensitive GlyRs by taurine or glycine primarily inhibits the hi gh K+-induced rise in [Ca2+](i), and subsequent release of vasopressin. Exp ression of GlyRs in vasopressin and oxytocin terminals is confirmed by immu nohistochemistry. Their implication in the osmoregulation of neurohormone s ecretion was assessed on isolated whole neurohypophyses. A 6.6% hypoosmotic stimulus reduces by half the depolarization-evoked vasopressin secretion, an inhibition totally prevented by strychnine. Most importantly, depletion of taurine by a taurine transport inhibitor also abolishes the osmo-depende nt inhibition of vasopressin release. Therefore, in the neurohypophysis, an osmoregulatory system involving pituicytes, taurine, and GlyRs is operatin g to control Ca2+ influx in and neurohormone release from nerve terminals. This elucidates the functional role of glial taurine in the neurohypophysis , reveals the expression of GlyRs on axon terminals, and further defines th e role of glial cells in the regulation of neuroendocrine function.