Osmoregulation of Vasopressin Secretion via Activation of Neurohypophysial Nerve Terminals Glycine Receptors by Glial Taurine

Abstract

Osmotic regulation of supraoptic nucleus (SON) neuron activity depends in part on activation of neuronal glycine receptors (GlyRs), most probably by taurine released from adjacent astrocytes. In the neurohypophysis in which the axons of SON neurons terminate, taurine is also concentrated in and osmo-dependently released by pituicytes, the specialized glial cells ensheathing nerve terminals. We now show that taurine release from isolated neurohypophyses is enhanced by hypo-osmotic and decreased by hyper-osmotic stimulation. The high osmosensitivity 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'-diisothiocyanatostilbene-2,2'-disulfonic acid suggests the involvement of volume-sensitive anion channels. On purified neurohypophysial nerve endings, activation of strychnine-sensitive GlyRs by taurine or glycine primarily inhibits the high K(+)-induced rise in [Ca(2+)](i) and subsequent release of vasopressin. Expression of GlyRs in vasopressin and oxytocin terminals is confirmed by immunohistochemistry. Their implication in the osmoregulation of neurohormone secretion was assessed on isolated whole neurohypophyses. A 6.6% hypo-osmotic 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-dependent inhibition of vasopressin release. Therefore, in the neurohypophysis, an osmoregulatory system involving pituicytes, taurine, and GlyRs is operating to control Ca(2+) 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 the role of glial cells in the regulation of neuroendocrine function.

Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens

“…Furthermore, it is likely that these glycine-and taurine-like receptors are the same entity because the existence of a specific taurine receptor has yet to be demonstrated. This idea is supported by the recent findings of Hussy et al (2001) who reported that taurine-mediated osmotic regulation in the neurohypophysis is exerted through glycine receptors. To date, no protein that could unequivocally account for this receptor has been identified and characterized.…”

A specific taurine recognition site in the rabbit brain is responsible for taurine effects on thermoregulation

“…Since taurine binds both to GABA A and GABA B receptors (Krogsgaard-Larsen et al, 1980;Kontro & Oja, 1990;Frosini et al, 2003), it may affect body temperature by interacting with GABA-ergic systems. However, there is a large body of evidence that taurine elicits a number of neurophysiological effects distinguishable from those afforded by GABA (Hayes et al, 1975;Huxtable, 1989;Kamisaki et al, 1993;Hussy et al, 2001;Tuz et al, 2001). Moreover, taurine desynchronizes while GABA, muscimol and baclofen synchronize motor and limbic cortex activity patterns, suggesting that their effects could depend on the interaction with different neuronal pathways afferent to the cortical areas monitored (Sgaragli et al, 1978;Sesti et al, 1999).…”

Desensitization of Homomeric α1 Glycine Receptor Increases with Receptor Density

“…Differences in GlyR kinetics depending on receptor density seem likely to affect glycine receptor function in both immature and mature brain. Interestingly, extrasynaptic GlyRs can be activated both by spillover of glycine from adjacent synapses (Faber and Korn, 1988) and by nonsynaptic release of taurine, in both immature animals and adults (Flint et al, 1998;Hussy et al, 2001). It is therefore important to determine how kinetics of currents at GlyRs varies as a function of their density, which is greater at synaptic than at nonsynaptic sites.…”