【作者】 金政；

【导师】 许文燮；

【作者基本信息】 延边大学 ， 生理学， 2006， 博士

【摘要】 非肾上腺能非胆碱能(non-adrenergic non-cholinergic，NANC)神经广泛分布在胃肠道，它们在胃肠道平滑肌运动的调节中起着重要作用。三磷酸腺苷(adenosine triphosphate，ATP)、一氧化氮(nitric oxide，NO)、血管活性肠肽(vasoactive intestinal peptide，VIP)、垂体腺苷酸环化酶激活肽(pituitary adenylate cyclase-activating peptide，PACAP)和一氧化碳(carbon monoxide，CO)等被认为是NANC抑制性神经递质或调质。自从1970年Burnstock和他的同事们首次提出ATP为NANC神经递质以来，许多研究支持这一假设。例如，在大鼠回肠和结肠等，许多神经纤维末梢含有ATP，但是关于ATP调节胃肠平滑肌运动方面，因动物和平滑肌种类不同，存在着不同的实验结果。在小鼠结肠和大鼠回肠平滑肌，嘌呤能P2Y受体介导平滑肌舒张，而P2X受体的激动剂α，β-MeATP(α，β-methylene ATP)或β，γ-MeATP(β，γ-methylene ATP)引起平滑肌细胞收缩。相反，在大鼠结肠平滑肌上发现，ATP通过嘌呤能P2Y受体引起平滑肌收缩。因此，尽管ATP及其嘌呤类拟似物是公认的胃肠道NANC神经递质之一，对于它们在调节胃肠运动方面的作用仍存在分歧。为此，本工作利用电生理学、药理学等方法在豚鼠胃窦环行肌上研究了嘌呤类受体的两种亚型P2X和P2Y受体在平滑肌运动和电活动中的作用，并初步探讨了它们的机制。实验结果如下： 一、内源性嘌呤类物质参与胃平滑肌运动调节 电场刺激是研究神经系统调节胃肠平滑肌运动作用及其机制的重要手段。首先，为了证实电场刺激胃平滑肌引起内在神经兴奋时哪些神经递质释放、平滑肌的运动有何改变，从中探讨了NANC的神经递质中是否也有嘌呤类递质参与的可能更多还原

【Abstract】 Gastrointestinal (GI) smooth muscles generally become relaxed when non-adrenergic non-cholinergic(NANC) nerves are stimulated. It has been considered that the relaxation is mediated by inhititory NANC neurotransmitters such as nitric oxide (NO), vasointestinal polypeptide (VIP), and adenosine 5’-triphosphate (ATP), which are released from enteric nerves of GI tract. Among them, ATP is now well established as an endogenous purinergic neurotransmitter on the GI tract and the urinary badder and as a cotransmitter of noradrenaline in sympathetic nerve theminals. Until now, ATP has been considered th most likely inhibitory NANC neurotransmitter in mammalian GI smooth muscles. Especially in th gastric fundus, ATP has been proposed as a major inhibitory neurotransmitter responsible for the receptive relaxation after meal. However, GI smooth muscles showed excitatory responses to ATP and its analogues in the guinea-pig ileum and in the rat colon muscalaris mucosae. In rat gastric fundus, exogenous ATP evoked abiphasic reponse, i.e., transient relaxation followed a by contraction. Consequently, these results imply that ATP acts not only as an inhibitory transmitter in GI smooth muscles.In order to investigate the role of non-adrenergic non-cholinergic nerves in regulating mechanical and electrical activity of gastric circular smooth muscle, the effects of ATP and its analogues on gastric motility and electrical activities were observed in guinea-pig. In organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured. Electrical activity of the muscle was recorded using intracellular microelectrode. Electrical and mechanical activities were recorded by chart recorder. Membrane currents were recorded using whole-cell patch clamp techenique.Results 1. Endogenous purinogic agonist involved in regulation of gastric motilityElectric field stimulation is impotant method in study effect of nervous system on GI smooth muscles motility. In order to determine what neurotransmitters released更多还原