Picomolar concentrations of L-dopa stereoselectively potentiate activities of presynaptic beta-adrenoceptors to facilitate the release of endogenous noradrenaline from rat hypothalamic slices.

Interactions between (-)-isoproterenol and DOPA on the release of endogenous noradrenaline (NA) evoked by electrical field stimulation (2 Hz, alternative polarity) were studied in rat superfused hypothalamic slices in the presence of 3-hydroxybenzylhydrazine, an inhibitor of L-aromatic amino acid decarboxylase, and cocaine. Isoproterenol (0.3-3 nM) facilitated the NA release in a concentration-dependent manner, while 10 pM L-DOPA alone produced no effect. This facilitation at 0.3-3 nM was potentiated by 20-70% by simultaneously applied 10 pM L-DOPA but that at 3 nM was not modified by 10 pM D-DOPA. This potentiation of the isoproterenol (3 nM)-induced facilitation of the NA release was concentration-dependent at 1-10 pM of L-DOPA. L-DOPA methyl ester (1 nM) antagonized the L-DOPA (10 pM)-induced potentiation of the facilitation of the NA release by 3 nM isoproterenol to a level of the facilitation by isoproterenol alone, whereas 10 nM (-) propranolol antagonized both the facilitation by isoproterenol alone and its potentiation by L-DOPA to a control level. Picomolar concentrations of L-DOPA stereoselectively act on a recognition site for itself, and then potentiate activities of presynaptic beta-adrenoceptors to facilitate the NA release from rat hypothalamic slices.