ROLE OF CARBOXYLESTERASES IN THE PREVENTION AND POTENTIATION OF N-METHYLCARBAMATE TOXICITY

被引:41
作者
GUPTA, RC
DETTBARN, WD
机构
[1] VANDERBILT UNIV,DEPT PHARMACOL,2100 PIERCE AVE,NASHVILLE,TN 37212
[2] MURRAY STATE UNIV,BREATHITT VET CTR,HOPKINSVILLE,KY
关键词
ACETYLCHOLINESTERASE; CARBOXYLESTERASE; N-METHYLCARBAMATES; INHIBITION OF ACETYLCHOLINESTERASE; INHIBITION OF CARBOXYLESTERASE; CARBOFURAN; PROPOXUR; ALDICARB; ISO-OMPA; PHYSOSTIGMINE; FALSE TARGET; SPECIFIC TARGET; POTENTIATION OF ANTI-ACHE AGENTS;
D O I
10.1016/0009-2797(93)90057-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pretreatment of rats with iso-OMPA one hour prior to each of the N-methylcarbamate insecticides, carbofuran, propoxur, or aldicarb, potentiated the toxicity of these carbamates threefold. None of these compounds alone in the dosage used produced toxic signs; however, carboxylesterase (CarbE) activity in a variety of organs including brain, muscle, liver, and plasma was significantly reduced, while acetylcholinesterase (AChE) activity was unchanged. Significant inhibition of AChE was observed after the combination of tetraisopropylpyro-phosphoramide (iso-OMPA) with each one of these N-methylcarbamates. It is suggested that CarbEs are more sensitive than AChE to these N-methylcarbamates and inhibition of CarbE by iso-OMPA raises the concentration of N-methylcarbamates available to inhibit AChE resulting in increased toxicity. Other N-methylcarbamates such as physostigmine do not inhibit CarbE, nor are their toxicities potentiated by iso-OMPA.
引用
收藏
页码:295 / 303
页数:9
相关论文
共 17 条
[1]  
BOSKOVIC B, 1979, ARCH TOXICOL, V42, P207
[2]  
CLEMENT JG, 1989, FUNDAM APPL TOXICOL, V4, pS96
[3]  
DETTBARN WD, 1989, ENZYMES HYDROLYSING ORGANOPHOSPHORUS COMPOUNDS, P165
[4]   OBSERVATIONS ON THE SPECIFICITY OF THE INHIBITION OF CHOLINESTERASES BY TRI-ORTHO-CRESYL PHOSPHATE [J].
EARL, CJ ;
THOMPSON, RHS ;
WEBSTER, GR .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1953, 8 (01) :110-114
[5]   CONCERTED ROLE OF CARBOXYLESTERASES IN THE POTENTIATION OF CARBOFURAN TOXICITY BY ISO-OMPA PRETREATMENT [J].
GUPTA, RC ;
KADEL, WL .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, 1989, 26 (04) :447-457
[6]   MECHANISMS INVOLVED IN THE DEVELOPMENT OF TOLERANCE TO DFP TOXICITY [J].
GUPTA, RC ;
PATTERSON, GT ;
DETTBARN, WD .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1985, 5 (06) :S17-S28
[7]   TOXIC INTERACTION OF TETRAISOPROPYLPYROPHOSPHORAMIDE AND PROPOXUR - SOME INSIGHTS INTO THE MECHANISMS [J].
GUPTA, RC ;
KADEL, WL .
ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 1990, 19 (06) :917-920
[8]  
GUPTA RC, 1991, PHARMACOLOGIST, V33, P164
[9]   TREATMENT OF POISONING BY SOMAN [J].
LEADBEATER, L ;
INNS, RH ;
RYLANDS, JM .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1985, 5 (06) :S225-S231
[10]  
MAXWELL DM, 1988, J PHARMACOL EXP THER, V246, P986