Nanomolar L-DOPA Facilitates Release of Dopamine via Presynaptic, β-Adrenoceptors: Comparative Studies on the Actions in Striatal Slices from Control and 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPTP)-Treated C57 Black Mice, an Animal Model for Parkinson's Disease

[摘要] References(23)Cited-By(17)Effects of L-DOPA (0.1-10, 000 nM) on spontaneous release (Sp), evoked release (S) and tissue content (C) of dopamine (DA) were studied comparatively in superfused striatal slices from control and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahy-dropyridine (MPTP)-treated C57 black mice to obtain evidence for L-DOPA-induced facilitation of S via presynaptic β-adrenoceptors. In control slices, isoproterenol-induced concentration-dependent increases in S were propranolol-sensitive. L-DOPA at 0.1-3 nM tended to increase the S of DA with a concomitant tendency of increases in Sp. L-DOPA at 10-1 × 104 nM concentration-dependently increased Sp. L-DOPA at 1-10 μM tended to increase S and 10 μM increased C. In slices from MPTP-treated mice, the absolute amounts of Sp, S and C decreased by half compared to those in control slices. L-DOPA at 3 nM facilitated S without increasing Sp. This facilitation was antagonized by propranolol at 3 nM. L-DOPA at 30 nM decreased S from the peak facilitation, which contrasted with no effect in the control slices. However, 10-100 nM L-DOPA increased Sp more markedly than that in the control slices. L-DOPA at 100 nM increased S and C, which contrasted with no effect in the control slices. In conclusion, nanomolar L-DOPA facilitates the S of DA via presynaptic β-adrenoceptors at concentrations lower than those required to induce conversion to DA even in striatal slices from the MPTP-treated mice model for Parkinson's disease. In model slices, susceptibilities of the Sp, S and C of DA to exogenous L-DOPA could be determined by a balance between degeneration-induced reduction in DOPA-decarboxylase activities and “up-regulation” on the activities of surviving DA neurons.

[学科分类] 药理学