Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen:: a new site of action of ethanol?

被引:19
作者
Darstein, M
Löschmann, PA
Knörle, R
Feuerstein, TJ
机构
[1] Univ Freiburg, Neurozentrum, Neurol Klin, Sekt Klin Neuropharmakol, D-79106 Freiburg, Germany
[2] Wyeth Pharma GmbH, Clin Res & Dev, D-48159 Munster, Germany
关键词
H-3]-acetylcholine release; Rat caudatoputamen; cholinergic intemeurons; glycine receptors; serine; strychnine; ethanol;
D O I
10.1007/PL00005112
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In the present study acute effects of ethanol on [H-3]-acetylcholine ([H-3]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [H-3]-ACh release (Ig EC50 = -4.10, CI95 = [-4.14, -4.05]) was inhibited by strychnine in a competitive manner (pA(2) = 6.86, CI95 = [6.61, 7.08]). Release of [H-3]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC50 = -2.61, CI95 = [-2.69, -2.52]), Both glycine and L-serine showed similar maximum effects (E-max(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) [1.09, 1.32]). Ethanol at concentrations of 2 parts per thousand (= 34 mM) and 4 parts per thousand (= 68 mM) inhibited glycine-evoked [H-3]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA, of ethanol was 1.19, CI95 = [0.85, 1.41], at 2 parts per thousand [v/v] and 1.51, CI95 = [1.19, 1.78] at 4 parts per thousand ethanol. Similar to its action on glycine-evoked [H-3]-ACh release, ethanol at 4 parts per thousand [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA(2) = 0.83, CI95 = [-0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [H-3]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.
引用
收藏
页码:738 / 745
页数:8
相关论文
共 38 条
[1]   The slope parameter of concentration-response curves used as a touchstone for the existence of spare receptors [J].
Agneter, E ;
Singer, EA ;
Sauermann, W ;
Feuerstein, TJ .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 356 (03) :283-292
[2]   THE MAMMALIAN GLYCINE RECEPTOR - BIOLOGY AND STRUCTURE OF A NEURONAL CHLORIDE CHANNEL PROTEIN [J].
BETZ, H ;
BECKER, CM .
NEUROCHEMISTRY INTERNATIONAL, 1988, 13 (02) :137-146
[3]   MECHANISM OF ANION PERMEATION THROUGH CHANNELS GATED BY GLYCINE AND GAMMA-AMINOBUTYRIC-ACID IN MOUSE CULTURED SPINAL NEURONS [J].
BORMANN, J ;
HAMILL, OP ;
SAKMANN, B .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 385 :243-286
[4]   CONFORMATIONALLY DEFINED NEUROTRANSMITTER ANALOGS - SELECTIVE-INHIBITION OF GLUTAMATE UPTAKE BY ONE PYRROLIDINE-2,4-DICARBOXYLATE DIASTEREOMER [J].
BRIDGES, RJ ;
STANLEY, MS ;
ANDERSON, MW ;
COTMAN, CW ;
CHAMBERLIN, AR .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (02) :717-725
[5]  
CURTIS DR, 1974, ERG PHYSIOL BIOL CH, V69, P97
[6]   PHARMACOLOGICAL STUDY OF RENSHAW CELL INHIBITION [J].
CURTIS, DR ;
GAME, CJA ;
LODGE, D ;
MCCULLOCH, RM .
JOURNAL OF PHYSIOLOGY-LONDON, 1976, 258 (01) :227-242
[7]  
Feuerstein TJ, 1996, N-S ARCH PHARMACOL, V354, P618
[8]  
FEUERSTEIN TJ, 1993, N-S ARCH PHARMACOL, V347, P171
[9]  
FEUERSTEIN TJ, 1994, N-S ARCH PHARMACOL, V350, P1
[10]   ETHANOL INHIBITS THE N-METHYL-D-ASPARTATE (NMDA)-INDUCED ATTENUATION OF THE NMDA-EVOKED NORADRENALINE RELEASE IN THE RAT-BRAIN CORTEX - INTERACTION WITH NMDA-INDUCED DESENSITIZATION [J].
FINK, K ;
GOTHERT, M .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1991, 344 (02) :167-173