Modulation of peristalsis by neurotensin and evidence for mechanism of generation, in the intestine

本研究旨在探讨内源性神经降压素(NT)是否参与肠蠕动的调节。在鸡的直肠中，NT的所有主要特征表明NT在兴奋性非肾上腺素能和非胆碱能(NANC)传递中可能起中介作用。在豚鼠中，NT分别存在于Remak神经节和NANC神经元细胞体和轴突终末所在的直肠中，NT引起肌膜去极化，NT具有取消直肠肌肉对NANC神经元刺激的反应以及自身多肽的能力。在豚鼠中，NT存在于Remak神经节和NANC神经元的细胞体和轴突终末所在的直肠中，NT导致肌膜去极化，NT具有取消直肠肌肉对NANC神经元刺激的反应和自身多肽的能力无论是直接作用还是间接作用，都可能参与肠道蠕动的调节。其主要作用是在蠕动波放电率较高的肠管上段起抑制作用，而在蠕动波放电率较低的肠段下段起兴奋作用，其收缩作用主要归因于小肠纵肌胆碱能神经释放ACh的间接作用。NT对大肠纵行肌、盲肠带绦虫和环行肌的收缩作用归因于直接作用。NT的松弛作用都归因于一种直接作用，并被阿帕明所阻断。膜片钳研究表明，NT通过G蛋白增加电压门控性钙通道的激活。在β-七叶皂甙皮肤的平滑肌中，NT通过释放钙离子库来加强卡巴胆碱和咖啡因引起的张力发展。这种增强作用可能是由于收缩元件对钙的敏感性增加所致，其中磷脂酶C通过百日咳毒素敏感的G蛋白激活和PKC被二酰甘油激活似乎是一种信号转导系统。

Our studies were designed to determine whether endogenous neurotensin (tridecapeptide) (NT) participates in the regulation of peristalsis of the intestine.In the rectum of the fowl, all of the major characteristics of NT suggest a possible role for NT as a mediator in the excitatory non-adrenergic and non-cholinergic (NANC) transmission : NT is present in Remak ganglia and the rectum in which cell bodies and axon terminals of NANC neurones are located, respectively, NT causes the muscle membrane to depolarize, and NT has an ability to abolish the responses of the rectal muscle to stimulation of NANC neurones as well as the peptide itself.In guinea-pig intestine, NT, whether acts directly or indirectly, may be involved in regulation of the peristalsis in the intestine. Its predominant effect is inhibitory in the upper region of the intestine in which discharge rate of peristaltic waves is higher, but excitatory in the lower region in which discharge rate of peristaltic waves is lower.NT owes the greater part of the contractile effect to an indirect action brought about by releasing ACh from cholinergic nerves in the longitudinal muscle of the small intestine. The contractile effects of NT on the longitudinal muscle of the large intestine, taenia caecum and circular muscle are attributable to a direct action. The relaxant effects of NT are all attributable to a direct action and blocked by apamin. Patch-clamp studies showed that NT produces an increase in activation of voltage-gated calcium cannel through a G-protein.In beta-escin-skinned smooth muscle, NT potentiates carbachol- and caffeine-induced tension developments brought about by release of Ca2+ stores. The potentiation may result from an increase in Ca2+ sensitivity of contractile elements, in which activation of phospholipase C through a pertussis toxin-sensitive G-protein and activation of PKC by diacylglycerol seem to be operated as a signal transduction system.