IL-1β and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig

IL-1β and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig
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DOI:
10.1046/j.1365-2982.2000.00228.x
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发表时间:
2000-12-01
影响因子:
3.5
通讯作者:
Tack, J
Tack, J
中科院分区:
医学3区
文献类型:
--
作者:
Kelles, A;Janssens, J;Tack, J

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在豚鼠回肠常规肌丛制备中,通过细胞内记录研究了炎症介质白细胞介素-1 β (IL-1 β)和白细胞介素-6 (IL-6)对肌肠神经元的影响。微压喷射IL-1 β和IL-6 (10(-7) mol L-1)分别对19%(13/70)和7%(5/70)的肌肠神经元产生兴奋作用。IL-1 β受体拮抗剂的灌注抑制了IL-1 β诱导的去极化。观察到的反应是抗河豚毒素的,表明直接的神经元效应。在一氧化氮合酶免疫反应以及胆碱乙酰转移酶免疫反应神经元中,可以看到对这两种细胞因子的反应。此外,IL-1 β和IL-6均可逆地引起胆碱能神经末梢乙酰胆碱释放的突触前抑制。两种细胞因子对慢兴奋性突触后电位无影响。因此,我们可以得出结论,炎症介质IL-1 β和IL-6可以通过对肌肠神经元亚群的直接兴奋作用和突触前抑制乙酰胆碱释放来作为胃肠道运动的兴奋性神经调节剂。
The effects of the inflammatory mediators interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) on myenteric neurones were investigated by intracellular recordings in a conventional myenteric plexus preparation of guinea pig ileum. Micropressure ejection of IL-1 beta and IL-6 (10(-7) mol L-1) both caused an excitatory effect in, respectively, 19% (13/70) and 7% (5/70) of the myenteric neurones. The IL-1 beta -induced depolarizations were inhibited by superfusion of the IL-1 beta receptor antagonist. The responses seen were tetrodotoxin-resistant, indicating a direct neuronal effect. Responses to both cytokines were seen in nitric oxide synthase-immunoreactive as well as choline acetyltransferase-immunoreactive neurones. In addition, both IL-1 beta and IL-6 reversibly caused a presynaptic inhibition of acetylcholine release from cholinergic nerve terminals. Both cytokines had no effect on the slow excitatory postsynaptic potentials. Therefore, we can conclude that the inflammatory mediators IL-1 beta and IL-6 can act as excitatory neuromodulators of gastrointestinal motility through direct excitatory actions on a subset of myenteric neurones and through the presynaptic inhibition of acetylcholine release.