L-DOPA Methyl Ester Antagpnizes Competitively L-DOPA-Induced Facilitation of Noradrenaline Release from Rat Hypothalamic Slices

Abstract

In rat hypothalamic slices, antagonism by L-DOPA methyl ester and (-)-propranolol against L-DOPA-induced facilitation of endogenous noradrenaline (NA) release was characterized under the inhibition of dopa-decarboxylase. L-DOPA at 10 nM to 1 PM facilitated the evoked NA release in a concentration-dependent manner. L-DOPA methyl ester (3, 10 and 30 nM) progressively shifted the concentration-release curve for L-DOPA to the right: Schild plots gave a straight line with a slope of 1.00 and pA., was 8.9. This antagonistic action was not mimicked by L-phenylalanine, a substrate for L-DOPA transport system. In contrast, 10 and 100 nM propranolol concentration-dependently reduced the maximal effect of L-DOPA without rightward shift of the concentration-release curve. L-DOPA methyl ester is a potent competitive antagonist for the action of L-DOPA, and the recognition site of L-DOPA differs from presynaptic β-adrenoceptors.