| Autor: |
Dong Chuan Zuo, Seok Choi, Pawan Kumar Shah, Man Yoo Kim, Chan Guk Park, Young Dae Kim, Jun Lee, In Yeoup Chang, Hak-Sun Lee, Su Cheong Yeom, Hey-Jung Moon, Seung-Yong Seong, Lnsuk So, Jae Yeoul Jun |
| Předmět: |
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| Zdroj: |
Pharmacology; 2012, Vol. 90 Issue 3/4, p151-159, 9p, 1 Chart, 6 Graphs |
| Abstrakt: |
Background and Purpose: 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. Methods: We performed whole-cell patch clamp and RT-PCR in cultured ICCs from mouse small intestine. Results: 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 E2 (PGE2)-EP2 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. Conclusions: LPS can activate ICCs to release NO and PGE2 through TLR4 activation. The released NO and PGE2 inhibit pacemaker currents by activating ATP-sensitive K+ channels. The LPS actions are mediated by tyrosine kinase signaling pathways. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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