L-dopa methyl ester antagonizes competitively L-dopa-induced facilitation of noradrenaline release from rat hypothalamic slices.
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 dopadecarboxylase. L-DOPA at 10 nM to 1 microM 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 pA2 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 beta-adrenoceptors.
Goshima
Y
Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Nakamura
S
S
Misu
Y
Y
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007980:Levodopa / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010649:Phenylalanine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats
D007980:Levodopa; D010649:Phenylalanine; D011433:Propranolol; C035420:levodopa methyl ester; D009638:Norepinephrine