Role of excitatory amino acid receptors in K+- and glutamate-evoked release of endogenous adenosine from rat cortical slices.
K+ and glutamate released endogenous adenosine from superfused slices of rat parietal cortex. The absence of Ca2+ markedly diminished K+- but not glutamate-evoked adenosine release. Tetrodotoxin decreased K+- and glutamate-evoked adenosine release by 40 and 20%, respectively, indicating that release was mediated in part by propagated action potentials in the slices. Inhibition of ecto-5'-nucleotidase by alpha,beta-methylene ADP and GMP decreased basal release of adenosine by 40%, indicating that part of the adenosine was derived from the extracellular metabolism of released nucleotide. In contrast, inhibition of ecto-5'-nucleotidase did not affect release evoked by K+ or glutamate, suggesting that adenosine was released as such. Inhibition of glutamate uptake by dihydrokainate potentiated glutamate-evoked release of adenosine. Glutamate-evoked adenosine release was diminished 50 and 55% by the N-methyl-D-aspartate (NMDA) receptor antagonists, DL-2-amino-5-phosphonovaleric acid and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), respectively. The remaining release in the presence of MK-801 was diminished a further 66% by the non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, suggesting that both NMDA and non-NMDA receptors were involved in glutamate-evoked adenosine release. Surprisingly, K+-evoked adenosine release was also diminished about 30% by NMDA antagonists, suggesting that K+-evoked adenosine release may be partly mediated indirectly through the release of an excitatory amino acid acting at NMDA receptors.
Hoehn
K
K
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
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TD
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D000241:Adenosine; D011188:Potassium; D002118:Calcium