6-OHDA-induced hemiparkinsonism and chronic L-DOPA treatment increase dopamine D1-stimulated [(3)H]-GABA release and [(3)H]-cAMP production in substantia nigra pars reticulata of the rat.
It has been proposed that striatonigral GABAergic transmission in the substantia nigra reticulata (SNr) is enhanced during Parkinson's disease and subsequent L-DOPA treatment. To evaluate this proposal we determined the effects of activating dopamine D1 receptors on depolarization induced [(3)H]-GABA release and on [(3)H]-cAMP accumulation in slices of SNr of rats with unilateral 6-OHDA lesions with and without l-DOPA treatment. Denervation increased depolarization induced D1-stimulated [(3)H]-GABA release, while repeated L-DOPA treatment further enhanced this response. Both also enhanced the effects of forskolin on [(3)H]-cAMP production and [(3)H]-GABA release, while neither modified the stimulating effects of 8-Br-cAMP on the release. These results shown that, after 6-OHDA lesions and l-DOPA treatment, cAMP signaling is enhanced. Furthermore, the results suggest that activation of sites in the signaling cascade downstream of cAMP synthesis is not required to increase release.
Rangel-Barajas
Claudia
C
Departamento de Fisiología, Biofísica y Neurociencias. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Apartado Postal 14-740, 07000 México D.F. México.
Silva
Isaac
I
García-Ramírez
Martha
M
Sánchez-Lemus
Enrique
E
Floran
Leonor
L
Aceves
Jorge
J
Erlij
David
D
Florán
Benjamín
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology*; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D010726:Phosphodiesterase Inhibitors; D017447:Receptors, Dopamine D1; D014316:Tritium; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine