Detrusor overactivity induced by intravesical application of adenosine 5′-triphosphate under different delivery conditions in rats
Detrusor overactivity induced by intravesical application of adenosine 5′-triphosphate under different delivery conditions in rats
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DOI：
10.1016/j.urology.2005.06.099
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发表时间：
2005-12-01
期刊：
影响因子：
2.1
通讯作者：
Yoshimura, N
中科院分区：
文献类型：
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作者：
Nishiguchi, J;Hayashi, Y;Yoshimura, N
目标.研究膀胱内应用三磷酸腺苷（ATP）对膀胱活动的影响，以阐明尿路上皮屏障功能和胞外ATP酶活性在ATP介导的逼尿肌过度活动机制中的作用。在清醒的雌性大鼠中，通过从膀胱顶插入膀胱内导管进行连续膀胱测压。ATP溶液调节到pH 6.0并没有引起显着的逼尿肌过度活动，在浓度为60 mM。然而，在膀胱预处理与硫酸鱼精蛋白（10毫克/毫升），以增加尿路上皮通透性，ATP溶液（pH 6.0）诱导逼尿肌过度活动，通过减少收缩间期。鱼精蛋白处理后ATIP的这些刺激作用可被P2 X受体拮抗剂如吡哆醛-5-磷酸-6-偶氮苯基-2 '，4-二磺酸（70 μ mol/kg）和2'，3 '-O-（2，4，6，三硝基苯基）ATP（30 μ mol/kg）拮抗。在全身性辣椒素（125 mg/kg皮下注射）预处理的大鼠中，这些也受到抑制。膀胱内输注4，4 '-二异硫氰酸二苯乙烯-2，2'-二磺酸（5 mM，pH 6.0）（一种胞外ATP酶抑制剂）后，α，β-亚甲基ATP（5 mM，pH 6.0）或ATP（60 mM，pH 6）诱导逼尿肌过度活动，而无需鱼精蛋白预处理，但收缩间期的缩短幅度小于鱼精蛋白处理后ATP的缩短幅度。膀胱上皮细胞的低通透性和胞外ATP酶活性可以阻止ATP激活上皮下P2 X受体，从而诱导膀胱过度活动。因此，由于尿路上皮损伤导致的内源性ATIP渗透增强可能导致过敏性膀胱疾病（如间质性膀胱炎）的尿频和膀胱疼痛。
Objectives. To investigate the effects of intravesical application of adenosine 5'-triphosphate (ATP) on bladder activity to elucidate the role of urothelial barrier function and ecto-ATPase activity in the ATP-mediated mechanism inducing detrusor overactivity.Methods. Continuous cystometry by an intravesical catheter inserted from the bladder dome was performed in conscious female rats.Results. ATP solutions adjusted to pH 6.0 did not elicit significant detrusor overactivity at a concentration of 60 mM. However, in bladders pretreated with protamine sulfate (10 mg/mL) to increase urothelial permeability, ATP solution (pH 6.0) induced detrusor overactivity by decreasing the intercontraction intervals. These irritant effects of ATIP after protamine treatment were antagonized by P2X receptor antagonists, such as pyridoxal-5-phosphate-6-azophenyl-2',4-disulfonic acid (70 mu mol/kg) and 2',3'-O-(2,4,6, trinitrophenyl) ATP (30 mu mol/kg). These were also suppressed in rats pretreated with systemic capsaicin (125 mg/kg subcutaneously). Alpha,beta-methylene ATP (5 mM, pH 6.0) or ATP (60 mM, pH6) after intravesical infusion of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (5 mM, pH 6.0), an ecto-ATPase inhibitor, induced detrusor overactivity without protamine pretreatment, but the reduction in intercontraction intervals was smaller compared with that with ATP after protamine treatment.Conclusions. Low permeability of bladder epithelium and ecto-ATPase activity can prevent ATP activation of subepithelial P2X receptors to induce bladder overactivity. Thus, enhanced penetration of endogenous ATIP owing to urothelial damage may contribute to urinary frequency and bladder pain in hypersensitive bladder disorders such as interstitial cystitis.