Glutamate-evoked release of endogenous adenosine from rat cortical synaptosomes is mediated by glutamate uptake and not by receptors.
L-Glutamate (10 microM-1 mM) released endogenous adenosine from rat cortical synaptosomes. Studies with excitatory amino acid antagonists, (+)-5-methyl-16,11,dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), 6,7-dinitroquinoxaline-2,3-dione (DNQX), Mg2+, and agonists N-methyl-D-aspartate (NMDA), kainate, and quisqualate, indicated that this release was not receptor mediated. D,L-2-Amino-4-phosphonobutanoic acid (APB) also did not affect glutamate-evoked adenosine release. Inhibition of glutamate uptake by dihydrokainate or replacement of extracellular Na+ blocked glutamate-evoked adenosine release. D-aspartate, which is a substrate for the glutamate transporter but is not metabolized, also released adenosine, suggesting that release was due to amino acid transport and not to its subsequent metabolism. D-Glutamate, a relatively poor substrate for the transporter, was correspondingly less potent than L-glutamate at releasing adenosine. Glutamate-evoked adenosine release was not Ca2+ dependent or tetrodotoxin sensitive and did not appear to occur on the bidirectional nucleoside transporter. Inhibition of ecto-5'-nucleotidase virtually abolished glutamate-evoked adenosine release, indicating that adenosine was derived from extracellular metabolism of released nucleotide(s). However, L-glutamate did not release ATP and did not appear to release cyclic AMP. Therefore, transport of glutamate into presynaptic terminals releases some other nucleotide which is converted extracellularly to adenosine. This adenosine could act at P1-purinoceptors to modulate glutamatergic neurotransmission.
Hoehn
K
K
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
White
T D
TD
D000241:Adenosine / Q000378:metabolism*; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid; D008565:Membrane Proteins / Q000502:physiology; D033703:Nucleoside Transport Proteins; D011687:Purines / Q000378:metabolism; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism*
D000596:Amino Acids; D002352:Carrier Proteins; D005971:Glutamates; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D011687:Purines; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D015222:Sodium Channels; D018698:Glutamic Acid; D000241:Adenosine; D002118:Calcium