Shiba Y, Mizumoto A, Satoh M, Inui A, Itoh Z, Omura S
Gastrointestinal Research Laboratories, Gunma University, Maebashi, Japan.
Gastroenterology. 1996 Jan;110(1):241-50. doi: 10.1053/gast.1996.v110.pm8536863.
BACKGROUND & AIMS: EM523, a nonpeptide motilin agonist, is being developed for clinical use to improve delayed gastric emptying. The aim of this study was to examine the effect of EM523 on endogenous release of gut and pancreatic hormones in conscious dogs.
Motility of the gastrointestinal tract was monitored using force transducers. Blood concentrations of gut and pancreatic hormones were measured using a specific radioimmunoassay. EM523 (3 micrograms/kg) or normal saline (5 mL) was given during the phase I period of the interdigestive state.
A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523. The significant release of these hormones was suppressed by pretreatment with atropine and completely eliminated by a 5-hydroxytryptamine 3 receptor antagonist and truncal vagotomy.
The findings suggest that EM523 stimulates the release of pancreatic polypeptide, insulin, and motilin by activating the cholinergic parasympathetic nerve system, finally stimulating the endocrine pancreas through vagally cholinergic muscarinic receptors in the pancreatic islets. The participation of 5-hydroxytryptamine 3 receptors in this system is strongly suggested by the results.
非肽类胃动素激动剂EM523正被开发用于临床，以改善胃排空延迟。本研究旨在检测EM523对清醒犬肠道和胰腺激素内源性释放的影响。
使用力传感器监测胃肠道的运动。采用特异性放射免疫分析法测定肠道和胰腺激素的血药浓度。在消化间期的I期给予EM523（3微克/千克）或生理盐水（5毫升）。
单次注射EM523总能在完整的胃窦诱发III期样收缩，并伴有胃动素、胰多肽和胰岛素的显著（P<0.01）释放；EM523未释放胰高血糖素、胃泌素、胆囊收缩素和促胰液素。这些激素的显著释放被阿托品预处理所抑制，并被5-羟色胺3受体拮抗剂和迷走神经干切断术完全消除。
研究结果表明，EM523通过激活胆碱能副交感神经系统刺激胰多肽、胰岛素和胃动素的释放，最终通过胰岛中的迷走神经胆碱能毒蕈碱受体刺激内分泌胰腺。结果强烈提示5-羟色胺3受体参与了该系统。
