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.
Goshima
Y
Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Nakamura
S
S
Ohno
K
K
Misu
Y
Y
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D006834:Hydrazines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013237:Stereoisomerism
D006834:Hydrazines; D011943:Receptors, Adrenergic, beta; D007980:Levodopa; D011433:Propranolol; C004297:3-hydroxybenzylhydrazine; D003042:Cocaine; D007545:Isoproterenol; C035420:levodopa methyl ester; D009638:Norepinephrine