Details

Autor(en) / Beteiligte

• Ueda, H
• Sato, K
• Okumura, F
• Inoue, A
• Nakata, Y
• Ozaki, N
• Yue, J.L.
• Misu, Y

Titel

Supersensitization of neurochemical responses by L-DOPA and dopamine receptor agonists in the striatum of experimental Parkinson's disease model rats

Ist Teil von

• Biomedicine & pharmacotherapy, 1995, Vol.49 (4), p.169-177

Ort / Verlag

France: Elsevier SAS

Erscheinungsjahr

1995

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• We studied the mechanisms of dopamine receptor agonist- and L-DOPA-mediated supersensitization in experimental Parkinson's disease model rats, by measuring in vivo acetylcholine (ACh) release, GTPase activities, and mRNA expression in the striatum of 6-hydroxydopamine-treated rats, D 1 agonist (SKF38393) and D 2/D 3, agonists (bromocriptine and quinpirole) showed more potent stimulation or inhibitions on ACh release in the model rat than in the control. However, quinpirole-evoked stimulation of GTPase activity was enhanced in the model rats, compared to the control, while there was no significant enhancement of the bromoeriptine-evoked stimulation. On the other hand, L-DOPA at 0.3–10 pM showed a biphasic action including significant inhibition on the GTPase activity in the lesioned striatal membranes, but not in the control. In the RNAase protection assay, neither D 1, D 2, Gi1α, GoAα nor Gsα mRNA expression in the model was significantly different from the control. These findings suggest that there is supersensitization of D 1 and D 2/D 3 receptors in the experimental Parkinson's disease model, while the upregulation of their receptors or GTP-binding proteins (G-proteins) to be coupled to their receptors is unlikely involved in major parts of such mechanisms. In addition, the present report provides the first evidence that L-DOPA mediates neurochemical responses in the plasma membranes, possibly through its receptor.