L-dopa stimulates the release of [3H]gamma-aminobutyric acid in the basal ganglia of 6-hydroxydopamine lesioned rats.
L-DOPA stimulated the K(+)-induced [3H]GABA (gamma-aminobutyric acid) release from slices of substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen isolated from the ipsilateral side of 6-hydroxydopamine-lesioned rats, but the release from ipsilateral subthalamic slices was not affected. In substantia nigra, L-DOPA stimulation (EC50 = 1 microM) of [3H]GABA release was dose-dependently blocked (IC50 = 0.1 microM for the stimulation caused by 10 microM L-DOPA) by the D1 antagonist SCH 23390, but was not affected by (-)-sulpiride, a D2 antagonist. SCH 23390 also blocked the stimulation in the other nuclei. The DOPA decarboxylase inhibitor NSD-1015 (500 microM) did not prevent the stimulation induced by L-DOPA in all of the studied nuclei. The results suggest that L-DOPA is able to activate D1 receptors located on the terminals of striatal projections via the dopamine formed by a decarboxylation mediated by an NSD-1015-resistant enzyme. Activation of the presynaptic D1 receptors results in stimulation of GABA release.
Aceves
J
J
Department of Physiology, Biophysics and Neurosciences, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico D.F.
Floran
B
B
Martinez-Fong
D
D
Sierra
A
A
Hernandez
S
S
Mariscal
S
S
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D001552:Benzazepines / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D018492:Dopamine Antagonists; D006834:Hydrazines / Q000494:pharmacology; D006892:Hydroxydopamines; D066298:In Vitro Techniques; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration; D016627:Oxidopamine; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001552:Benzazepines; D018492:Dopamine Antagonists; D006834:Hydrazines; D006892:Hydroxydopamines; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D016627:Oxidopamine; C004297:3-hydroxybenzylhydrazine; D011188:Potassium