Tyrosine phosphorylation modulates the osmosensitivity of volume-dependenttaurine efflux from glial cells in the rat supraoptic nucleus

In the supraoptic nucleus, taurine, selectively released in an osmodependen t manner by glial cells through volume-sensitive anion channels, is likely to inhibit neuronal activity as part of the osmoregulation of vasopressin r elease. We investigated the involvement of various kinases in the activatio n of taurine efflux by measuring [H-3]taurine release from rat acutely isol ated supraoptic nuclei. The protein tyrosine kinase inhibitors genistein and tyrphostin B44 specifi cally reduced, but did not suppress, both the basal release of taurine and that evoked by a hypotonic stimulus. Inhibition of tyrosine phosphatase by orthovanadate had the opposite effect. The tyrosine kinase and phosphatase inhibitors shifted the relationship bet ween taurine release and medium osmolarity in opposite directions, suggesti ng that tyrosine phosphorylation modulates the osmosensitivity of taurine r elease, but is not necessary for its activation. Genistein also increased the amplitude of the decay of the release observed during prolonged hypotonic stimulation. Potentiation of taurine release by tyrosine kinases could serve to maintain a high level of taurine release i n spite of cell volume regulation. Taurine release was unaffected by inhibitors and/or activators of PKA, PKC, MEK and Rho kinase. Our results demonstrate a unique regulation by protein tyrosine kinase of t he osmosensitivity of taurine efflux in supraoptic astrocytes. This points to the presence of specific volume-dependent anion channels in these cells, or to a specific activation mechanism or regulatory properties. This may r elate to the particular role of the osmodependent release of taurine in thi s structure in the osmoregulation of neuronal activity.