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替仑西平、哌仑西平与阿托品对组胺、五肽胃泌素、氨甲酰甲胆碱、假饲及进食所引起胃酸和胃蛋白酶分泌的影响比较

Comparison of telenzepine, pirenzepine and atropine on gastric acid and pepsin secretion in response to histamine, pentagastrin, bethanechol, sham-feeding and feeding.

作者信息

Konturek S J, Tasler J, Cieszkowski M, Szewczyk K, Kromer W

机构信息

Institute of Physiology, Academy of Medicine, Krakow, Poland.

出版信息

Digestion. 1989;44(2):66-78. doi: 10.1159/000199894.

Abstract

This study was designed to compare gastric antisecretory effects of telenzepine, a new antimuscarinic agent, with those of pirenzepine and atropine in dogs. None of these antimuscarinics affected gastric acid secretion induced by histamine but all of them caused a dose-dependent inhibition of acid secretion from the gastric fistula (GF) and Heidenhain pouches (HP) stimulated by pentagastrin and bethanechol, telenzepine being 5-9 times more potent than pirenzepine and equipotent with atropine. All antimuscarinics were also effective inhibitors of acid responses to sham feeding and ordinary feeding. The inhibitory effect of telenzepine and pirenzepine were not accompanied by any major alterations in plasma gastrin or somatostatin but those of atropine were related to significant increase in plasma gastrin and to significant decrease in plasma somatostatin levels, suggesting the involvement of M2 receptors in the cholinergic control of these hormones. All three antimuscarinics were effective inhibitors of pepsin secretion induced both from the GF and HP by all secretagogues used. Neither telenzepine nor pirenzepine administered in various doses affected the heart rate while atropine caused a significant increase in heart rate confirming that the former agents are selective M1 receptor antagonists. This study provides evidence that telenzepine is more potent than pirenzepine in the inhibition of gastric secretion induced by pentagastrin, bethanechol, sham-feeding and ordinary feeding and that, unlike atropine, it does not increase plasma gastrin responses to meat feeding. In fact, telenzepine and pirenzepine alike reduced plasma gastrin concentrations under these conditions. No influence of these antimuscarinics on plasma somatostatin levels was observed.

摘要

本研究旨在比较新型抗毒蕈碱药物替仑西平与哌仑西平和阿托品对犬胃酸分泌的抑制作用。这些抗毒蕈碱药物均不影响组胺诱导的胃酸分泌,但它们都能剂量依赖性地抑制由五肽胃泌素和氨甲酰甲胆碱刺激胃瘘(GF)和海登海因小胃(HP)引起的胃酸分泌,替仑西平的效力比哌仑西平强5 - 9倍,与阿托品相当。所有抗毒蕈碱药物对假饲和正常进食引起的胃酸反应也均有抑制作用。替仑西平和哌仑西平的抑制作用并未伴随血浆胃泌素或生长抑素的任何重大变化,但阿托品的抑制作用与血浆胃泌素显著升高和血浆生长抑素水平显著降低有关,提示M2受体参与了这些激素的胆碱能调控。所有三种抗毒蕈碱药物对所有所用促分泌剂诱导的GF和HP胃蛋白酶分泌均有抑制作用。不同剂量的替仑西平和哌仑西平均不影响心率,而阿托品可使心率显著增加,证实前两者为选择性M1受体拮抗剂。本研究提供的证据表明,替仑西平在抑制五肽胃泌素、氨甲酰甲胆碱、假饲和正常进食诱导的胃酸分泌方面比哌仑西平更有效,且与阿托品不同,它不会增加血浆胃泌素对肉类进食的反应。事实上,在这些条件下,替仑西平和哌仑西平均可降低血浆胃泌素浓度。未观察到这些抗毒蕈碱药物对血浆生长抑素水平有影响。

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