Glutamate receptor activation induces carrier mediated release of endogenous GABA from rat striatal slices.
The regulation of striatonigral and striatopallidal GABAergic neurons by glutamatergic afferents is thought to play a critical role in normal basal ganglia function. Here we report that in striatal slices about 17% of K(+)-induced endogenous GABA release was Ca(2+)-independent and this could be blocked by a GABA transport inhibitor. Activation of N-methyl-D-aspartate (NMDA)- and quisqualate-sensitive receptors induced endogenous GABA efflux only in the presence of a GABA transaminase inhibitor; this efflux was inhibited by 60-80% with a GABA transport inhibitor. NMDA-induced GABA release was blocked by phencyclidine, Mg2+ and CGS 19755. Quisqualate-induced GABA release was blocked completely by a combination of the metabotropic antagonist, L-AP3 and CNQX, a non-NMDA receptor antagonist. These data indicate that excitatory amino acid agonists-induced GABA release is distinct from that induced by high K+ depolarization.
Wang
J
J
Department of Pharmacology, University of Texas Medical Branch, Galveston USA.
Lonart
G
G
Johnson
K M
KM
D000818:Animals; D002118:Calcium / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D018377:Neurotransmitter Agents; D009557:Nipecotic Acids; D010091:Oximes; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C078793:NNC 711; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D002118:Calcium