L-DOPA FACILITATES THE RELEASE OF ENDOGENOUS NOREPINEPHRINE AND DOPAMINE VIA PRESYNAPTIC BETA-1-ADRENOCEPTORS AND BETA-2-ADRENOCEPTORS UNDER ESSENTIALLY COMPLETE INHIBITION OF L-AROMATIC AMINO-ACID DECARBOXYLASE IN RAT HYPOTHALAMIC SLICES

被引:42
作者
GOSHIMA, Y
NAKAMURA, S
MISU, Y
机构
[1] Department of Pharmacology, Yokohama City University School of Medicine, Yokohama
关键词
D O I
10.1254/jjp.53.47
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In rat hypothalamic slices, L-aromatic amino acid decarboxylase (AADC) was assayed, and the actions of L-DOPA on impulse (2 Hz)-evoked norepinephrine (NE) and dopamine (DA) release were studied under inhibition of AADC. Slices were incubated with L-DOPA, and DA and NE produced by conversion of the precursor were analyzed by high performance liquid chromatography with electrochemical detection (HPLC-ECD). In the slices, the Km and Vmax of AADC were 131 μM and 122 pmol/min/mg protein, respectivelv. NSD-1015, an AADC inhibitor, caused a noncompetitive type of inhibition, and the Ki value was 0.086 μM. In the presence of 20 μM NSD-101 5, which was expected to cause 99.6% inhibition of AADC, L-DOPA (0.01-100 nM) concentration-dependently facilitated the release of NE from the superfused slices, and the L-DOPA (10 nM)-induced facilitation was antagonized by 100 nM ICI 89,406 and 100 nM ICI 118,551, a selective μ1 and μ2-adrenoceptor antagonist, respectively. This action of L-DOPA was not modified by 30/M tropolone, an inhibitor of catechol-O-methyl-transferase. L-DOPA at 0.01-1 nM similarly facilitated the release of DA. A quantitative analysis revealed that the L-DOPA-induced increase in NE and DA release was much higher by a factor of 3 to 4 ordres than was the amount of DA and NE converted from L-DOPA. These results add further support to the hypothesis that L-DOPA itself acts as a neuroactive substance in the rat central nervous system. © 1990, The Japanese Pharmacological Society. All rights reserved.
引用
收藏
页码:47 / 56
页数:10
相关论文
共 31 条
[1]  
AXELROD J, 1958, J BIOL CHEM, V233, P702
[2]  
BAKER RG, 1970, J PHARMACOL EXP THER, V173, P212
[3]   THE PHARMACOLOGY OF A BETA-2-SELECTIVE ADRENOCEPTOR ANTAGONIST (ICI-118,551) [J].
BILSKI, AJ ;
HALLIDAY, SE ;
FITZ GERALD, JD ;
WALE, JL .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (03) :430-437
[4]   INHIBITION OF DECARBOXYLASE OF AROMATIC AMINO ACIDS BY 2,3,4-TRIHYDROXYBENZYLHYDRAZINE + ITS SERYL DERIVATIVE [J].
BURKARD, WP ;
PLETSCHER, A ;
GEY, KF .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1964, 107 (02) :187-&
[5]  
Carlsson A., 1964, PROGR BRAIN RES, V8, P9
[6]   ACCUMULATION OF DOPAMINE IN PARENCHYMA AFTER DECARBOXYLASE INHIBITION IN CAPILLARIES OF BRAIN [J].
CONSTANT.J ;
BARTHOLI.G ;
TISSOT, R ;
PLETSCHE.A .
EXPERIENTIA, 1968, 24 (02) :130-&
[7]   THE DETERMINATION OF ENZYME INHIBITOR CONSTANTS [J].
DIXON, M .
BIOCHEMICAL JOURNAL, 1953, 55 (01) :170-171
[8]   (+/)(IODO-125)CYANOPINDOLOL, A NEW LIGAND FOR BETA-ADRENOCEPTORS - IDENTIFICATION AND QUANTITATION OF SUBCLASSES OF BETA-ADRENOCEPTORS IN GUINEA-PIG [J].
ENGEL, G ;
HOYER, D ;
BERTHOLD, R ;
WAGNER, H .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1981, 317 (04) :277-285
[9]  
GOLDBERG LI, 1972, PHARMACOL REV, V24, P1
[10]  
GOSHIMA Y, 1988, Japanese Journal of Pharmacology, V46, p104P