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Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway.

Abstract：

:Uropathogenic Escherichia coli is a common cause of urinary tract infection. We determined the effects of intravesical instillation of E. coli lipopolysaccharide (LPS, endotoxin) on muscle contractions, protein kinase C (PKC) translocation, and inducible nitric oxide synthase (iNOS) expression in rat urinary bladder. The contractions of the isolated rat detrusor muscle evoked by electrical field stimulations were measured short-term (1 h) or long-term (24 h) after intravesical instillation of LPS. One hour after LPS intravesical instillation, bladder PKC-alpha translocation from cytosolic fraction to membrane fraction and endothelial (e)NOS protein was elevated, and detrusor muscle contractions were significantly increased. PKC inhibitors chelerythrine and Ro32-0432 inhibited this LPS-enhanced contractile response. Application of PKC activator beta-phorbol-12,13-dibutyrate enhanced the muscle contractions. Three hours after intravesical instillation of LPS, iNOS mRNA was detected in the bladder. Immunoblotting study also demonstrated that the induction of iNOS proteins is detected in bladder in which LPS was instilled. 24 h after intravesical instillation of LPS, PKC-alpha translocation was impaired in the bladder; LPS did not affect PKC-delta translocation. Muscle contractions were also decreased 24 h after LPS intravesical instillation. Aminoguanidine, a selective iNOS inhibitor, blocked the decrease in PKC-alpha translocation and detrusor contractions induced by LPS. These results indicate that there are different mechanisms involved in the alteration of urinary bladder contractions after short-term and long-term treatment of LPS; an iNOS-regulated PKC signaling may participate in causing the inhibition of muscle contractions in urinary bladder induced by long-term LPS treatment.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Weng TI,Chen WJ,Liu SH

doi

10.1016/j.taap.2005.02.005

subject

Has Abstract

pub_date

2005-10-15 00:00:00

pages

163-9

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(05)00065-7

journal_volume

208

pub_type

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Bladder instillation of Escherichia coli lipopolysaccharide alters the muscle contractions in rat urinary bladder via a protein kinase C-related pathway.