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由于抑制蛋白质合成,环己酰亚胺具有胃抗分泌活性。

Gastric antisecretory activity of cycloheximide due to inhibition of protein synthesis.

作者信息

Im W B, Davis J P, Blakeman D P, Sachs G, Robert A

出版信息

Biochim Biophys Acta. 1987 May 29;899(2):285-94. doi: 10.1016/0005-2736(87)90410-x.

DOI:10.1016/0005-2736(87)90410-x
PMID:3034329
Abstract

Treatment of rats with cycloheximide 1 h before carbachol dose-dependently reduced the secretagogue-stimulated gastric acid secretion in pylorus ligated rats, and partially blocked carbachol- or histamine-induced activation of rat gastric (H+ + K+)-ATPase which includes translocation of reserve intracellular (H+ + K+)-ATPase into the apical membrane of the parietal cells and induction of a KCl pathway. Time-course studies showed that the drug was effective only when administered at least 30 min before the secretagogues. Puromycin showed the same effect as cycloheximide. Pulse labelling studies with [35S]methionine led to identification of two most actively synthesized polypeptides in rat gastric mucosa; the proteins of 38,000 and 14,000 molecular weight. The larger polypeptide was identified as rat pepsinogen. The identity of the smaller protein is not known yet. We suggest that synthesis of nascent polypeptide(s) is required for certain steps of the acid secretory process leading to the activation of the acid pump.

摘要

在给予卡巴胆碱前1小时用放线菌酮处理大鼠,可剂量依赖性地降低幽门结扎大鼠中促分泌剂刺激的胃酸分泌,并部分阻断卡巴胆碱或组胺诱导的大鼠胃(H⁺+K⁺)-ATP酶的激活,这包括储备细胞内(H⁺+K⁺)-ATP酶向壁细胞顶膜的转运以及KCl途径的诱导。时间进程研究表明,该药物仅在促分泌剂给药前至少30分钟给药时才有效。嘌呤霉素显示出与放线菌酮相同的效果。用[³⁵S]甲硫氨酸进行的脉冲标记研究导致在大鼠胃黏膜中鉴定出两种合成最活跃的多肽;分子量为38,000和14,000的蛋白质。较大的多肽被鉴定为大鼠胃蛋白酶原。较小蛋白质的身份尚不清楚。我们认为,新生多肽的合成是导致酸泵激活的酸分泌过程某些步骤所必需的。

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