Wang Guo-Du, Wang Xi-Yu, Hu Hong-Zhen, Fang Xiu-Cai, Liu Sumei, Gao Na, Xia Yun, Wood Jackie D
Dept. of Physiology and Cell Biology, The Ohio State University, College of Medicine and Public Health, Columbus, OH 43210, USA.
Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G614-26. doi: 10.1152/ajpgi.00119.2005.
Actions of ANG II on electrical and synaptic behavior of enteric neurons in the guinea pig small intestine were studied. Exposure to ANG II depolarized the membrane potential and elevated neuronal excitability. The number of responding neurons was small, with responses to ANG II in 32% of submucosal neurons and 25% of myenteric neurons. Hyperpolarizing responses were evoked by ANG II in 45% of the neurons. The hyperpolarizing responses were suppressed by alpha2-noradrenergic receptor antagonists, which suggested that the hyperpolarizing responses reflected stimulation of norepinephrine release from sympathetic neurons. Exposure to ANG II enhanced the amplitude and prolonged the duration of noradrenergic inhibitory postsynaptic potentials and suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. The selective ANG II(1) receptor (AT1R) antagonists, ZD-7115 and losartan, but not a selective AT2R antagonist (PD-123319), suppressed the actions of ANG II. Western blot analysis and RT-PCR confirmed expression of AT1R protein and the mRNA transcript for the AT1R in the enteric nervous system. No expression of AT2R protein or mRNA was found. Immunoreactivity for AT1R was expressed by the majority of neurons in the gastric antrum and small and large intestine. AT1R immunoreactivity was coexpressed with calbindin, choline acetyltransferase, calretinin, neuropeptide Y, and nitric oxide synthase in subpopulations of neurons. The results suggest that formation of ANG II might have paracrine-like actions in the enteric nervous system, which include alterations in neuronal excitability and facilitated release of norepinephrine from sympathetic postganglionic axons. The enhanced presence of norepinephrine is expected to suppress fast and slow excitatory neurotransmission in the enteric microcircuits and to suppress neurogenic mucosal secretion.
研究了血管紧张素II（ANG II）对豚鼠小肠肠神经元电活动和突触行为的作用。暴露于ANG II使膜电位去极化并提高神经元兴奋性。反应性神经元数量较少，32%的黏膜下神经元和25%的肌间神经元对ANG II有反应。45%的神经元中ANG II诱发超极化反应。α2-去甲肾上腺素能受体拮抗剂可抑制超极化反应，这表明超极化反应反映了交感神经元去甲肾上腺素释放的刺激。暴露于ANG II可增强去甲肾上腺素能抑制性突触后电位的幅度并延长其持续时间，同时抑制快速和慢速兴奋性突触后电位的幅度。选择性ANG II（1）受体（AT1R）拮抗剂ZD-7115和氯沙坦可抑制ANG II的作用，而选择性AT2R拮抗剂（PD-123319）则无此作用。蛋白质印迹分析和逆转录聚合酶链反应证实了肠神经系统中AT1R蛋白和AT1R mRNA转录本的表达。未发现AT2R蛋白或mRNA的表达。胃窦、小肠和大肠中的大多数神经元表达AT1R免疫反应性。在神经元亚群中，AT1R免疫反应性与钙结合蛋白、胆碱乙酰转移酶、钙视网膜蛋白、神经肽Y和一氧化氮合酶共表达。结果表明，ANG II的形成可能在肠神经系统中具有旁分泌样作用，包括改变神经元兴奋性和促进交感神经节后轴突去甲肾上腺素的释放。去甲肾上腺素的增加预计会抑制肠微回路中的快速和慢速兴奋性神经传递，并抑制神经源性黏膜分泌。
