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Potentiation by Thrombin of Hyposmotic Glutamate and Taurine Efflux from Cultured Astrocytes: Signalling Chains

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Abstract

Activation of protein-activated receptor (PAR-1) by thrombin potentiates the hyposmotic efflux of 3H-d-aspartate and 3H-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.

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Acknowledgements

The authors acknowledge the valuable technical assistance of Claudia Peña Segura and Gerardo Ramos Mandujano. This work was supported by grants No. 46465 from CONACYT, México and IN209507 from DGAPA, UNAM.

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Authors and Affiliations

  1. Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico, DF, 04510, Mexico

    S. Cruz-Rangel, R. Hernández-Benítez, E. Vázquez-Juárez, A. López-Dominguez & H. Pasantes-Morales

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  1. S. Cruz-Rangel
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  2. R. Hernández-Benítez
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  3. E. Vázquez-Juárez
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  4. A. López-Dominguez
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  5. H. Pasantes-Morales
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Corresponding author

Correspondence to H. Pasantes-Morales.

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Special issue article in honor of Dr. Ricardo Tapia.

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Cruz-Rangel, S., Hernández-Benítez, R., Vázquez-Juárez, E. et al. Potentiation by Thrombin of Hyposmotic Glutamate and Taurine Efflux from Cultured Astrocytes: Signalling Chains. Neurochem Res 33, 1518–1524 (2008). https://doi.org/10.1007/s11064-008-9632-x

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  • DOI: https://doi.org/10.1007/s11064-008-9632-x

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