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Pasantes Morales, H; Cruz-Rangel, S; Hernandez-Benitez, R; Vazquez-Juarez, E; Lopez-Dominguez, A (2008)

POTENTIATION BY THROMBIN OF HYPOSMOTIC GLUTAMATE AND TAURINE EFFLUX FROM CULTURED ASTROCYTES: SIGNALLING CHAINS

NEUROCHEM RES 33(8):1518-1524
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Activation of protein-activated receptor (PAR-1) by thrombin potentiates the hyposmotic efflux of H-3-D-aspartate and H-3-taurine from cultured cerebellar astrocytes. This effect is mediated by a thrombin-elicited increase in cytosolic Ca2+ levels [Ca2+](i) and the activation of phosphoinositide-3-kinase (PI3K). These signalling pathways operate independently showing additive effects if prevented simultaneously. The contribution of the Ca2+-mediated pathway to thrombin-increased D-aspartate or taurine efflux, evaluated by the inhibitory effect of preventing [Ca2+](i) rise, was higher for D-aspartate (64% efflux decrease) than for taurine (40% decrease). The PI3K blocker decreased 48% and 36% D-aspartate and taurine efflux, respectively. Hyposmolarity increases phosphorylation of EGFR and c-src, but thrombin did not enhance this effect. Blockade of EGFR/src phosphorylation marginally reduced (11-14%) the hyposmolarity plus thrombin efflux of D-aspartate; taurine efflux was more sensitive to these blockers (18-26%). Since thrombin has no effect increasing EGFR/src phosphorylation in astrocytes, the contribution of this transactivation pathway may represent the inhibition of the hyposmotic efflux solely.