Action of lipopolysaccharide on interstitial cells of cajal from mouse small intestine.
OBJECTIVE
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.
Departments of Physiology, College of Medicine, Chosun University, Gwangju, Korea.
Dong Chuan
DC
Zuo
Seok
S
Choi
Pawan Kumar
PK
Shahi
Man Yoo
MY
Kim
Chan Guk
CG
Park
Young Dae
YD
Kim
Jun
J
Lee
In Yeoup
IY
Chang
Hak-Sun
HS
Lee
Su Cheong
SC
Yeom
Hey-Jung
HJ
Moon
Seung-Yong
SY
Seong
Insuk
I
So
Jae Yeoul
JY
Jun
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000502:physiology; D054086:KATP Channels / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology
D054086:KATP Channels; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone