MEPACRINE-INDUCED INHIBITION OF THE INWARD CURRENT MEDIATED BY 5-HT3 RECEPTORS IN RAT NODOSE GANGLION NEURONS

被引:9
作者
FAN, P
机构
[1] Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, 20852
关键词
NODOSE GANGLION; MEPACRINE; QUINACRINE; 5-HT3; RECEPTOR; PATCH-CLAMP;
D O I
10.1111/j.1476-5381.1994.tb13141.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 With the whole-cell patch clamp technique, the effect of the antimalarial drug, mepacrine (quinacrine) on the inward current mediated by 5-HT3 receptors (5-hydroxytryptamine (5-HT)-induced current) was investigated in isolated nodose ganglion neurones of the rat. 2 5-HT and the selective 5-HT3 receptor agonists, 2-methyl-5-HT and m-chlorophenylbiguanide elicited an inward current which reversed at around 0 mV and quickly desensitized to a steady state level. 3 Mepacrine dose-dependently inhibited the peak current induced by 5-HT with an IC50 of 2.1 mu M and an apparent Hill coefficient of 0.99. 4 Mepacrine increased the decay rate of the 5-HT-induced current. 5 The effect of mepacrine on the 5-HT-induced current was reversible and not dependent on membrane potential. The reversal potential of the 5-HT-induced current was not affected. 6 Intracellular mepacrine had no significant effect on the 5-HT-induced current and did not block the extracellular action of mepacrine. 7 Concentration-response curves in the presence and absence of mepacrine suggest a non-competitive inhibition of 5-HT-induced current by mepacrine.
引用
收藏
页码:745 / 748
页数:4
相关论文
共 26 条
[1]  
ANDERSON DC, 1983, MOL PHARMACOL, V24, P48
[2]  
BILLAH MM, 1981, J BIOL CHEM, V256, P5399
[3]   DISTRIBUTION AND METABOLISM OF ARACHIDONIC-ACID IN RABBIT PLATELETS DURING AGGREGATION AND ITS MODIFICATION BY DRUGS [J].
BLACKWELL, GJ ;
DUNCOMBE, WG ;
FLOWER, RJ ;
PARSONS, MF ;
VANE, JR .
BRITISH JOURNAL OF PHARMACOLOGY, 1977, 59 (02) :353-366
[4]  
CHIARIELLO M, 1987, J PHARMACOL EXP THER, V241, P560
[5]  
COX RN, 1985, J BIOL CHEM, V260, P7186
[6]   ACCESSIBILITY OF DNA INSITU TO VARIOUS FLUOROCHROMES - RELATIONSHIP TO CHROMATIN CHANGES DURING ERYTHROID-DIFFERENTIATION OF FRIEND-LEUKEMIA CELLS [J].
DARZYNKIEWICZ, Z ;
TRAGANOS, F ;
KAPUSCINSKI, J ;
STAIANOCOICO, L ;
MELAMED, MR .
CYTOMETRY, 1984, 5 (04) :355-363
[7]   SIMULTANEOUS ANALYSIS OF FAMILIES OF SIGMOIDAL CURVES - APPLICATION TO BIOASSAY, RADIOLIGAND ASSAY, AND PHYSIOLOGICAL DOSE-RESPONSE CURVES [J].
DELEAN, A ;
MUNSON, PJ ;
RODBARD, D .
AMERICAN JOURNAL OF PHYSIOLOGY, 1978, 235 (02) :E97-E102
[8]   INTERACTION OF BASIC COMPOUNDS WITH COATED VESICLES [J].
DICERBO, A ;
NANDI, PK ;
EDELHOCH, H .
BIOCHEMISTRY, 1984, 23 (25) :6036-6040
[9]  
Fan P., 1993, Society for Neuroscience Abstracts, V19, P282
[10]  
Fan P., 1992, Society for Neuroscience Abstracts, V18, P800