Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats
| العنوان: | Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats |
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| المؤلفون: | Akihito Iwami, Katsuaki Ito, Masahiro Ikeda, Hiromi Katsura |
| المصدر: | Naunyn-Schmiedeberg's Archives of Pharmacology. 377:483-490 |
| بيانات النشر: | Springer Science and Business Media LLC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | medicine.medical_specialty, medicine.drug_class, media_common.quotation_subject, Pharmacology, urologic and male genital diseases, Urination, Rats, Sprague-Dawley, chemistry.chemical_compound, Phenols, Internal medicine, Cystitis, Purinergic P2 Receptor Antagonists, medicine, Animals, Polycyclic Compounds, heterocyclic compounds, PPADS, Oxybutynin, Cyclophosphamide, media_common, Dose-Response Relationship, Drug, medicine.diagnostic_test, Urinary Bladder, Overactive, Chemistry, Purinergic receptor, Antagonist, Cystometry, General Medicine, Receptor antagonist, medicine.disease, Rats, Disease Models, Animal, Endocrinology, Overactive bladder, Pyridoxal Phosphate, Injections, Intravenous, Mandelic Acids, Female, Receptors, Purinergic P2X3, Receptors, Purinergic P2X2, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1432-1912 0028-1298 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::371b1c88d2e83dc5d8eab5839ef8db26Test https://doi.org/10.1007/s00210-007-0197-zTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....371b1c88d2e83dc5d8eab5839ef8db26 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321912 00281298 |
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