Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine.
Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine.
复制标题
缓激肽对豚鼠小肠肌间神经丛神经元电和突触行为的作用。
DOI：
10.1038/sj.bjp.0705180
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Wood,JackieD
中科院分区：
文献类型：
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作者：
Hu,Hong-Zhen;Liu,Sumei;Gao,Na;Xia,Yun;Mostafa,Randa;Ren,Jun;Zafirov,DimiterH;Wood,JackieD
用电生理方法研究缓激肽（BK）对离体豚鼠小肠肌间神经丛神经元的作用。暴露于BK使AH-和S-型神经元的膜电位去极化和兴奋性升高。与去极化反应相关的神经元输入电阻在S-型中降低或不变，在AH-型中增加。选择性B2 BK受体拮抗剂HOE-140抑制BK诱发反应，而选择性B1受体拮抗剂des-arg 10-HOE-140则不抑制BK诱发反应。RT-PCR证实了B2受体mRNA的表达，但未证实B1受体mRNA的表达。荧光标记的HOE-140（HOE 741）的结合定位于整体封片制备物中的神经节细胞。BK B2受体与钙结合蛋白或一氧化氮合酶共表达，BK可抑制快、慢兴奋性突触后电位的振幅。BK不降低应用5-羟色胺或P物质引起的去极化反应和烟碱对乙酰胆碱的反应。这表明BK对神经传递的作用是突触前抑制神经递质的释放。浴槽液中存在HOE-140可抑制或消除BK的突触前抑制作用。环氧合酶抑制剂吡罗昔康可抑制BK的直接兴奋作用及其突触前抑制作用。应用前列腺素E_2、D_2、F_2 α或I_2可模拟BK诱发的反应，结果提示BK作用于肌间神经元上的B_2BK受体，刺激肾上腺素的形成。一旦形成并释放，所述阿糖胞苷就用于提高肌间神经丛中神经节细胞的兴奋性并抑制神经递质的突触释放（British Journal of Pharmacology（2003）138，1221-1232）。doi：10.1038/sj.bjp.0705180
Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea‐pig small intestinein vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH‐ and S‐type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S‐type and increased in AH‐type neurones.The selective B2BK receptor antagonist HOE‐140, but not the selective B1receptor antagonist des‐arg10‐HOE‐140, suppressed the BK‐evoked responses. RT‐PCR confirmed the expression of B2receptor mRNA, but not B1receptor mRNA.Binding of fluorescently‐ labeled HOE‐140 (HOE741) was localized to ganglion cells in whole‐mount preparations. BK B2receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase.Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE‐140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK.The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E2, D2, F2αor I2mimicked the BK‐evoked responses.The results suggest that BK acts at B2BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.British Journal of Pharmacology(2003)138, 1221–1232. doi:10.1038/sj.bjp.0705180