Inhibition of tyrosine phosphorylation attenuates amino acid neurotransmitter release from the ischemic/reperfused rat cerebral cortex.
Protein tyrosine phosphorylation plays an important role in neuronal function. In this study we have examined the effects of inhibition of tyrosine phosphorylation on the extracellular levels of four neurotransmitter amino acids (aspartate, glutamate, gamma-aminobutyric acid (GABA) and glycine) and of the non-transmitter amino acid phosphoethanolamine during cerebral ischemia and reperfusion in a rat four vessel occlusion model. In comparison with the control group, the tyrosine kinase inhibitor genistein significantly depressed ischemia/reperfusion-evoked efflux of these amino acids, with the exception of GABA, into cerebral cortical superfusates. GABA efflux was non-significantly reduced. These results suggest that tyrosine phosphorylation is involved in the ischemia-evoked efflux of amino acids into the extracellular milieu, likely as a consequence of the phosphorylation of microtubule-associated protein kinase (MAP kinase) and downstream activation of PLA2 in the plasma membrane. Amino acid efflux would occur, in part, as a consequence of the ensuing disruption of plasma membrane integrity and leakage of cytoplasmic constituents along their concentration gradients.
Phillis
J W
JW
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Song
D
D
O'Regan
M H
MH
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014443:Tyrosine / Q000187:drug effects*
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007529:Isoflavones; D018377:Neurotransmitter Agents; D014443:Tyrosine; D019833:Genistein