Departments of Physiology, College of Medicine, Chosun University, Gwangju, Korea.
Pharmacology. 2012;90(3-4):151-9. doi: 10.1159/000340018. Epub 2012 Aug 7.
Lipopolysaccharide (LPS) induces intestinal dysmotility by alteration of smooth muscle and enteric neuronal activities. However, there is no report on the modulatory effects of LPS on the interstitial cells of Cajal (ICCs). We investigated the effect of LPS and its signal transduction in ICCs.
We performed whole-cell patch clamp and RT-PCR in cultured ICCs from mouse small intestine.
LPS suppressed the generation of pacemaker currents of ICCs. The mRNA transcripts for Toll-like receptor 4 (TLR4) were expressed in ICCs. However, the inhibitory action of LPS on pacemaker currents from TLR4(+/+) mice was not present in TLR4(-/-) mice. The inhibitory effects of LPS on ICCs were blocked by glibenclamide (an inhibitor of ATP-sensitive K(+) channels), NS-398 (a COX-2 inhibitor), AH6808 [a prostaglandin E(2) (PGE(2))-EP(2) receptor antagonist], ODQ (an inhibitor of guanylate cyclase) and L-NAME [an inhibitor of nitric oxide synthase (NOS)]. Furthermore, genistein and herbimycin A (tyrosine kinase inhibitors) blocked the LPS-induced inhibitory action on pacemaker activity in ICCs.
LPS can activate ICCs to release NO and PGE(2) through TLR4 activation. The released NO and PGE(2) inhibit pacemaker currents by activating ATP-sensitive K(+) channels. The LPS actions are mediated by tyrosine kinase signaling pathways.
脂多糖（LPS）通过改变平滑肌和肠神经元的活动引起肠道动力障碍。然而，目前尚无 LPS 对 ICC（Cajal 间质细胞）调节作用的报道。我们研究了 LPS 及其在 ICC 中的信号转导对 ICC 的影响。
我们在从小鼠小肠培养的 ICC 中进行全细胞膜片钳和 RT-PCR。
LPS 抑制 ICC 起搏电流的产生。Toll 样受体 4（TLR4）的 mRNA 转录本在 ICC 中表达。然而，LPS 对 TLR4（+/+）小鼠起搏电流的抑制作用在 TLR4（-/-）小鼠中不存在。LPS 对 ICC 的抑制作用被格列本脲（ATP 敏感性 K+通道抑制剂）、NS-398（COX-2 抑制剂）、AH6808[前列腺素 E2（PGE2）-EP2 受体拮抗剂]、ODQ（鸟苷酸环化酶抑制剂）和 L-NAME[一氧化氮合酶（NOS）抑制剂]阻断。此外，染料木黄酮和 herbimycin A（酪氨酸激酶抑制剂）阻断了 LPS 对 ICC 起搏活性的抑制作用。
LPS 可通过 TLR4 激活激活 ICC 释放 NO 和 PGE2。释放的 NO 和 PGE2 通过激活 ATP 敏感性 K+通道抑制起搏电流。LPS 作用是通过酪氨酸激酶信号通路介导的。
