Uropathogenic Escherichia coli alters muscle contractions in rat urinary bladder via a nitric oxide synthase-related signaling pathway.
BACKGROUND
Uropathogenic Escherichia coli (UPEC) is a common cause of urinary-tract infection. The mechanisms by which bacteria cause the symptoms of cystitis remain unclear.


METHODS
The contractions of isolated rat detrusor strips evoked by electrical field stimulations (EFS) or by exogenous agonists and immunoblotting for the detection of protein expression in the bladder were measured in the short (1 h) and long (24 h) term after the intravesical instillation of J96 (O4:K6) strain or UPEC isolated from patients with acute E. coli pyelonephritis or E. coli lipopolysaccharide (LPS).


RESULTS
One hour after the instillation of UPEC, the level of endothelial nitric oxide synthase (eNOS) and the contractile response, but not protein kinase C (PKC) and extracellular signal-regulated kinase (ERK)-1/2 activation, were higher. Twenty-four hours after UPEC treatment, detrusor contractions were decreased, and inducible (i) NOS protein expression and ERK1/2 phosphorylation, but not PKC activation, were observed. Both aminoguanidine and PD98059 treatment markedly reversed the decrease of EFS- and acetylcholine-evoked detrusor contractions induced by UPEC. The instillation of LPS triggered PKC activation but not ERK1/2 phosphorylation.


CONCLUSIONS
Short-term intravesical instillation of UPEC enhances detrusor contractions through an eNOS-related pathway, but iNOS-regulated ERK1/2 signaling may be involved in long-term UPEC treatment-induced responses. There are different mechanisms involved in the responses induced by UPEC and LPS.
Weng
Te I
TI
Department of Emergency Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10043, Taiwan.
Chen
Wen Jone
WJ
Wu
Hsiao Yi
HY
Liu
Shing-Hwa
SH
D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D001743:Urinary Bladder / Q000378:metabolism* / Q000503:physiopathology; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000503:physiopathology
D019001:Nitric Oxide Synthase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3