Role of the metabotropic P2Y(4) receptor during hypoglycemia: cross talk with the ionotropic NMDAR1 receptor

Experimental Cell Research
F CavaliereC Volonté

Abstract

It is well established that both extracellular ATP and glutamate exert a critical role during metabolic impairment, that several P2 receptor subunits are directly involved in this action and that a strong relationship exists between glutamatergic and purinergic signals. Therefore, here we studied the molecular behavior of the purinergic metabotropic P2Y(4) and the glutamatergic ionotropic NMDAR1 receptors during hypoglycemic cell death. We find that these proteins are oppositely modulated during glucose starvation (P2Y(4) is induced, whereas NMDAR1 is inhibited) and that both P2 and NMDA antagonists can restore basal protein expression levels. Moreover, double immunofluorescence experiments with confocal laser microscopy reveal co-localization at the membrane level between the P2Y(4) and NMDAR1 receptors, in both homologous (cerebellar granule neurons) and heterologous (Hek-293) cellular systems. This is furthermore confirmed by co-immunoprecipitation experiments. Finally, when we express the P2Y(4) receptor in the heterologous SH-SY5Y neuronal cell line, hypoglycemia then causes severe cell death and simultaneous downregulation of the NMDAR1 protein. In summary, our work establishes a potential molecular interplay between P2Y(...Continue Reading

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Citations

Jan 26, 2010·Cellular and Molecular Neurobiology·Juliana Karl FrizzoMarcos Emílio Frizzo
Apr 12, 2008·Purinergic Signalling·Nadia D'AmbrosiCinzia Volonté
Aug 10, 2010·The Cerebellum·Raphaël CourjaretJoachim W Deitmer
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May 8, 2007·Biochimica Et Biophysica Acta·Nadia D'AmbrosiCinzia Volonté
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Apr 13, 2007·Physiological Reviews·Geoffrey Burnstock
Jul 11, 2007·The Journal of Pharmacology and Experimental Therapeutics·Fabio CavaliereCinzia Volonté

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