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

我们的研究旨在确定内源性神经降压素是否在鸡的直肠中，NT的所有主要特征表明，NT可能在兴奋性非肾上腺素能和非胆碱能（NANC）传递中作为介体发挥作用：NT存在于Remak神经节和直肠，其中NANC神经元的胞体和轴突终末分别位于其中，NT引起肌膜脱髓鞘，在豚鼠小肠中，NT可能直接或间接地参与调节肠粘膜的增生。NT的主要作用是在蠕动波放电率较高的肠上段抑制，而在蠕动波放电率较低的肠下段兴奋，NT的收缩作用大部分是通过小肠纵肌胆碱能神经释放ACh而产生的间接作用。NT对大肠纵行肌、盲肠带和环行肌的收缩作用是直接作用。NT的舒张作用均为直接作用，并被apamin阻断。膜片钳研究表明，NT通过G蛋白增加电压门控钙通道的激活。在β-七叶皂苷皮肤的平滑肌中，NT增强卡巴胆碱和咖啡因诱导的张力发展，这是由Ca 2+储存的释放引起的。这种增强作用可能是由于收缩元件的Ca 2+敏感性增加，其中通过百日咳毒素敏感的G蛋白激活磷脂酶C和通过二酰基甘油激活PKC似乎作为信号转导系统操作。

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.