GABAB receptor activation partially inhibits N-methyl-D-aspartate-mediated tyrosine hydroxylase stimulation in rat striatal slices.
The effect of the GABAB agonist, (+/-)-baclofen, on the N-methyl-D-aspartate (NMDA)-mediated stimulation of tyrosine hydroxylase activity was investigated in slices of rat striatum. Tyrosine hydroxylase activity was stimulated by NMDA in a concentration-dependent manner (EC50, 1.3 +/- 0.3 microM; maximum stimulation 194 +/- 7% of basal activity). The action of NMDA was reversed by the NMDA antagonist, 2-amino-5-phosphonovalerate (AP-5). (+/-)-Baclofen (100 microM) decreased the maximum effect of NMDA by 24 +/- 2% without significantly modifying its EC50. The IC50 for the inhibitory action of (+/-)-baclofen was 4.2 +/- 1.2 microM. These results show that GABAB receptor activation modulates NMDA-stimulated tyrosine hydroxylase activity, further supporting the possibility of a role of GABA in the regulation of striatal dopaminergic neurotransmission.
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional de México.
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Arias Montaño
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Martínez-Fong
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Aceves
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D011963:Receptors, GABA-A; D016202:N-Methylaspartate; D014446:Tyrosine 3-Monooxygenase; D001418:Baclofen