Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677481 (urinary frequency)
 1,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is suggested that ATP and purinergic P2X receptors are involved in overactive bladder. In this study, we investigated the effect of the recently developed P2X3 and P2X2/3 receptor antagonist A-317491 on cyclophosphamide (CYP)-induced cystitis to determine whether a P2X receptor antagonist could be beneficial for the treatment of bladder overactivity induced by CYP. Female Sprague-Dawley (SD) rats were given 150 mg/kg CYP (i.p.). When the micturition activity was observed for 24 h in a conscious and unrestrained condition, CYP-treated rats exhibited increased urinary frequency. Two days after CYP injection, cystometry was performed in conscious rats, in which the bladder was continuously infused with saline (5 ml/h). In CYP-treated rats, non-voiding contractions were interposed between micturitions, suggestive of hyper-reflexia. Intravenous administration of A-317491 (20 or 50 mg/kg) or pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium (PPADS; a nonselective purinergic receptor antagonist, 10 mg/kg) prolonged the interval of voiding contraction and reduced the non-voiding contractions. On the other hand, oxybutynin (1 mg/kg), a muscarinic receptor antagonist, did not affect the frequency of non-voiding or voiding contractions in CYP-treated rats. A-317491 at the higher dose decreased the amplitude of voiding contractions, but increased the micturition volume. The residual urine in the bladder increased after treatment with CYP; A-317491 and PPADS reduced this, whereas oxybutynin had no effect. These data suggest that A-317491 is effective at improving the signs of CYP-induced cystitis and that the P2X3 or P2X2/3 receptor pathway is involved in bladder overactivity observed during CYP-induced cystitis.
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PMID:Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats. 1791 16

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6-S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.
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PMID:Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense. 3327 25