Effect of protein kinase C activation on N-methyl-D-aspartate-evoked release of adenosine and [3H]Norepinephrine from rat cortical slices.
The role of protein kinase C (PKC) in the N-methyl-D-aspartate (NMDA)-evoked release of adenosine (ADO) and [3H]norepinephrine (NE) from slices of rat parietal cortex was studied. In the absence of Mg++, the PKC activator phorbol 12-myristate 13-acetate (1 microM, PMA) did not release either ADO or [3H]NE, but it potentiated the release of ADO evoked by 20 microM NMDA and the release of -3H-NE evoked by 100 microM NMDA. These potentiating effects of PMA on the NMDA-evoked release of ADO and [3H]NE were reversed by the PKC inhibitor GF109,203X (1 microM). GF109,203X by itself had no effect on the NMDA-evoked release of either ADO or [3H]NE. In the presence of Mg++, PMA did not permit the NMDA-evoked release of [3H]NE to occur. These results indicate that PKC does not play an essential role in the NMDA-evoked release of either ADO or NE. However, activation of PKC potentiates the release of ADO and NE evoked by submaximal concentrations of NMDA. Activation of PKC will have the effect of increasing the inhibitory threshold provided by released ADO when only a few NMDA receptors are activated and will promote and accelerate excitatory responses when most of the available NMDA receptors become activated.
Wang
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Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
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D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D007211:Indoles; D008301:Maleimides; D016202:N-Methylaspartate; D011493:Protein Kinase C; D008274:Magnesium; D000241:Adenosine; C070515:bisindolylmaleimide I; D009638:Norepinephrine