亮氨酸-13-胃动素（KW-5139）诱发兔十二指肠肠神经元释放乙酰胆碱。

The Leu13-motilin (KW-5139)-evoked release of acetylcholine from enteric neurones in the rabbit duodenum.

作者信息

Kitazawa T, Ishii A, Taniyama K

机构信息

Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo. Co. Ltd., Shizuoka, Japan.

出版信息

Br J Pharmacol. 1993 May;109(1):94-9. doi: 10.1111/j.1476-5381.1993.tb13536.x.

DOI:10.1111/j.1476-5381.1993.tb13536.x

PMID:8495250

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2175567/

Abstract

Involvement of cholinergic mechanisms in the contractile response to Leu13-motilin (LMT, KW-5139) was investigated in rabbit duodenal segments, and longitudinal muscle-myenteric plexus (LM-MP) preparations preincubated wtih [3H]-choline. 2. Contractile response to LMT (0.1 nM-1 microM) consisted of an initial rapid (phasic) contraction and a tonic contraction slowly fading to a sustained plateau. LMT caused a concentration-dependent phasic contraction of rabbit isolated duodenal segments. The EC50 value was 2.5 nM and the maximum amplitude of the contraction was 103% of the response induced by acetylcholine (ACh, 100 microM). Neither tetrodotoxin nor atropine changed the EC50 value or the maximum amplitude of the response to LMT. 3. Both atropine and tetrodotoxin decreased the amplitude and accelerated fading of the tonic contraction produced by LMT. 4. LMT (30 nM-3 microM) induced an increase of 3H-outflow, in a concentration-dependent manner. The LMT-induced increase of 3H-outflow was prevented by removal of external Ca2+ or by the presence of tetrodotoxin. 5. Porcine motilin (10 nM-1 microM) also stimulated the release of 3H at a similar concentration-range to that seen with LMT. 6. Pretreatment with LMT (3 microM for 20 min) decreased LMT- and the porcine motilin-evoked release of 3H but did not alter the high K(+)-evoked release. 7. Our results suggest that LMT and porcine motilin stimulate the release of ACh from enteric neurones through the same receptor, and that the release of ACh plays a role in tonic components of contraction in the rabbit duodenum.

摘要

在兔十二指肠段以及预先用[3H]-胆碱孵育的纵行肌-肌间神经丛（LM-MP）标本中，研究了胆碱能机制在对亮氨酸13-胃动素（LMT，KW-5139）收缩反应中的作用。2. 对LMT（0.1 nM - 1 microM）的收缩反应包括初始的快速（相性）收缩和逐渐消退至持续平台期的强直性收缩。LMT引起兔离体十二指肠段浓度依赖性的相性收缩。半数有效浓度（EC50）值为2.5 nM，收缩的最大幅度为乙酰胆碱（ACh，100 microM）诱导反应的103%。河豚毒素和阿托品均未改变对LMT反应的EC50值或最大幅度。3. 阿托品和河豚毒素均降低了LMT产生的强直性收缩的幅度并加速了其消退。4. LMT（30 nM - 3 microM）以浓度依赖性方式诱导3H外流增加。去除细胞外Ca2+或存在河豚毒素可阻止LMT诱导的3H外流增加。5. 猪胃动素（10 nM - 1 microM）在与LMT相似的浓度范围内也刺激3H释放。6. 用LMT（3 microM，处理20分钟）预处理可降低LMT和猪胃动素诱发的3H释放，但不改变高钾诱发的释放。7. 我们的结果表明，LMT和猪胃动素通过相同受体刺激肠神经元释放ACh，并且ACh的释放在兔十二指肠收缩的强直性成分中起作用。