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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-6
pubmed:dateCreated
2008-6-19
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
377
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
483-90
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17917716-Animals, pubmed-meshheading:17917716-Cyclophosphamide, pubmed-meshheading:17917716-Cystitis, pubmed-meshheading:17917716-Disease Models, Animal, pubmed-meshheading:17917716-Dose-Response Relationship, Drug, pubmed-meshheading:17917716-Female, pubmed-meshheading:17917716-Injections, Intravenous, pubmed-meshheading:17917716-Mandelic Acids, pubmed-meshheading:17917716-Phenols, pubmed-meshheading:17917716-Polycyclic Compounds, pubmed-meshheading:17917716-Purinergic P2 Receptor Antagonists, pubmed-meshheading:17917716-Pyridoxal Phosphate, pubmed-meshheading:17917716-Rats, pubmed-meshheading:17917716-Rats, Sprague-Dawley, pubmed-meshheading:17917716-Receptors, Purinergic P2X2, pubmed-meshheading:17917716-Receptors, Purinergic P2X3, pubmed-meshheading:17917716-Urinary Bladder, Overactive
pubmed:year
2008
pubmed:articleTitle
Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats.
pubmed:affiliation
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Miyazaki, 889-2192, Japan. itokt@cc.miyazaki-u.ac.jp
pubmed:publicationType
Journal Article