Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon
Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon
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DOI：
10.1152/ajpgi.00448.2009
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发表时间：
2010-07-01
影响因子：
4.5
通讯作者：
Jimenez, Marcel
中科院分区：
文献类型：
--
作者：
Gil, Victor;Gallego, Diana;Jimenez, Marcel
[10]杨文，王文.嘌呤能和氮能神经肌肉传递介导大鼠结肠神经元自发活动。美国生理学杂志胃肠和肝脏生理学299：G158-G169，2010。首次发表于2010年4月15日; doi：10.1152/ajpgi.00448.2009。一氧化氮（NO）和ATP介导胃肠道平滑肌松弛。然而，这些神经递质参与自发神经元活动是未知的。本工作的目的是研究大鼠结肠中段的自发神经肌肉传递。微电极实验进行恒定拉伸下，在圆周和纵向方向。记录自发抑制性连接电位（sIJP）。河豚毒素（1 μ M）和蜂毒肽（1 μ M）去极化平滑肌细胞和抑制sIJP。N-ω-硝基-L-精氨酸（L-NNA，1 mM）使平滑肌细胞去极化，但不修饰sIJP。相反，P2 Y（1）拮抗剂MRS-2500（1 μ M）不改变静息膜电位（RMP），但降低sIJP（IC 50 = 3.1 nM）。六甲铵（200 μ M）、NF-023（10 μ M）和昂丹司琼（1 μ M）不改变RMP和sIJP。这些结果与体外（肌肉浴）和体内（应变计）数据相关，其中L-NNA而不是MRS-2500诱导自发运动的持续增加。我们的结论是，在大鼠结肠，抑制性神经元调节平滑肌RMP和导致sIJP。在体外，抑制性神经递质的释放不依赖于烟碱、P2 X和5-羟色胺3型受体。神经元NO引起持续的平滑肌超极化，这是负责持续抑制自发运动。相反，作用于P2 Y（1）受体的ATP负责sIJP，但不介导抑制性神经张力。ATP和NO在调节胃肠运动中具有互补的生理功能。
Gil V, Gallego D, Grasa L, Martin MT, Jimenez M. Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon. Am J Physiol Gastrointest Liver Physiol 299: G158-G169, 2010. First published April 15, 2010; doi:10.1152/ajpgi.00448.2009.-Nitric oxide (NO) and ATP mediate smooth muscle relaxation in the gastrointestinal tract. However, the involvement of these neurotransmitters in spontaneous neuronal activity is unknown. The aim of the present work was to study spontaneous neuromuscular transmission in the rat midcolon. Microelectrode experiments were performed under constant stretch both in circular and longitudinal directions. Spontaneous inhibitory junction potentials (sIJP) were recorded. Tetrodotoxin (1 mu M) and apamin (1 mu M) depolarized smooth muscle cells and inhibited sIJP. N-omega-nitro-L-arginine (L-NNA, 1 mM) depolarized smooth muscle cells but did not modify sIJP. In contrast, the P2Y(1) antagonist MRS-2500 (1 mu M) did not modify the resting membrane potential (RMP) but reduced sIJP (IC50 = 3.1 nM). Hexamethonium (200 mu M), NF-023 (10 mu M), and ondansetron (1 mu M) did not modify RMP and sIJP. These results correlate with in vitro (muscle bath) and in vivo (strain gauges) data where L-NNA but not MRS-2500 induced a sustained increase of spontaneous motility. We concluded that, in the rat colon, inhibitory neurons regulate smooth muscle RMP and cause sIJP. In vitro, the release of inhibitory neurotransmitters is independent of nicotinic, P2X, and 5-hydroxytryptamine type 3 receptors. Neuronal NO causes a sustained smooth muscle hyperpolarization that is responsible for a constant inhibition of spontaneous motility. In contrast, ATP acting on P2Y(1) receptors is responsible for sIJP but does not mediate inhibitory neural tone. ATP and NO have complementary physiological functions in the regulation of gastrointestinal motility.