Picomolar concentrations of l-DOPA stereoselectively potentiate activities of presynaptic β-adrenoceptors to facilitate the release of endogenous noradrenaline from rat hypothalamic slices

Abstract

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 β-adrenoceptors to facilitate the NA release from rat hypothalamic slices.