Action of lipopolysaccharide on interstitial cells of cajal from mouse small intestine.

Abstract:

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 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. CONCLUSIONS: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.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Zuo DC,Choi S,Shahi PK,Kim MY,Park CG,Kim YD,Lee J,Chang IY,Lee HS,Yeom SC,Moon HJ,Seong SY,So I,Jun JY

doi

10.1159/000340018

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

151-9

issue

3-4

eissn

0031-7012

issn

1423-0313

pii

000340018

journal_volume

90

pub_type

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