CONVERSION OF METHYL-2-ACETOXYETHYL-2'-CHLOROETHYLAMINE TO AN ACETYLCHOLINE-LIKE AZIRIDINIUM ION AND ITS ACTION ON ISOLATED GUINEA-PIG ILEUM
CONVERSION OF METHYL-2-ACETOXYETHYL-2'-CHLOROETHYLAMINE TO AN ACETYLCHOLINE-LIKE AZIRIDINIUM ION AND ITS ACTION ON ISOLATED GUINEA-PIG ILEUM
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DOI：
10.1139/y72-116
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发表时间：
1972-01-01
影响因子：
2.1
通讯作者：
JACKSON, CH
中科院分区：
文献类型：
--
作者：
HIRST, M;JACKSON, CH
甲基-2-乙酰氧基乙基-2 ′-氯乙胺（乙酰胆碱-芥子气）在水溶液中异构化形成环状离子N-甲基-N-（2-乙酰氧基乙基）氮丙啶鎓，其结构类似于乙酰胆碱。它是豚鼠回肠的强效刺激剂，在pH 7.4时效力约为乙酰胆碱的六分之一，在pH 8.4时效力约为三分之一。激动剂活性可被阿托品、乙酰胆碱酯酶预孵育和硫代硫酸根离子预处理抑制。甲吡胺不抑制兴奋剂action.1小时暴露回肠段乙酰胆碱-芥子气浓度超过那些产生最大的反应，随后1小时的恢复期，没有产生突触后受体烷基化的证据。 处理后的反应乙酰胆碱略有抑郁症，但这些减少与孵育浓度的激动剂卤代烷基胺。毛果芸香碱诱导的反应未被这种处理改变，而5-羟色胺反应轻微增强，组胺反应轻微且不一致地改变。这些处理产生持续的、剂量相关的肌张力增加，这种作用与自发释放的乙酰胆碱的积累一致，可能是由原位乙酰胆碱酯酶抑制引起的。表面上，证据表明乙酰胆碱样氮丙啶离子可以刺激但不抑制豚鼠回肠的毒蕈碱受体。
Methyl-2-acetoxyethyl-2′-chloroethylamine (acetyicholine-mustard) isomerizes in aqueous solution to form a cyclic ion,N-methyl-N-(2-acetoxyethyl)aziridinium, which structurally resembles acetylcholine. It is a potent stimulant of the guinea pig ileum, being approximately one-sixth as potent as acetylcholine at pH 7.4 and one-third as potent at pH 8.4. The agonist activity is inhibited by atropine, by preincubation with acetylcholinesterase, and pretreatment with thiosulfate ion. Mepyramine does not inhibit the stimulant action.One hour exposures of ileum segments to concentrations of acetylcholine-mustard in excess of those producing maximal responses, followed by a 1 h recovery period, did not produce evidence of postsynaptic receptor alkylation. Post-treatment responses to acetylcholine were slightly depressed, but these reductions were not related to the incubation concentrations of the agonist haloalkylamine. Pilocarpine-induced responses were unaltered by this treatment whereas 5-hydroxytryptamine responses were slightly potentiated and histamine responses were slightly and inconsistently modified.These treatments produced persistent, dose-related increases in muscle tone, an effect consistent with accumulations of spontaneously liberated acetylcholine and possibly caused by inhibition ofin situacetylcholinesterase.Ostensibly, the evidence suggests that the acetylcholine-like aziridinium ion can stimulate, but not inhibit, the muscarinic receptors of the guinea pig ileum.