Khattab M, AL-Shabanah O, EL-Kashef H
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, P.O. Box 2457, Kingdom of Saudi Arabia.
Pharmacol Res. 2002 Feb;45(2):93-9. doi: 10.1006/phrs.2001.0916.
The present study was designed to investigate the effect and possible mechanism(s) of action of ATP and diadenosine tetraphosphate (AP(4)A) on the isolated rat urinary bladder rings. ATP ( 0.1- 1 x 10(-3)M) or AP(4)A ( 0.01- 0.1 x 10(-3)M) produced contractions of the isolated bladder rings in a concentration-dependent manner. The contraction-induced by AP(4)A in the bladder rings was approximately ten times more potent than that produced by ATP. Addition of ATP prior to addition of AP(4)A or vice versa desensitized bladder tissue to the second agonist with great reduction in the contraction produced. Electrical field stimulation (EFS, 40 V, 0.5 ms, 2 Hz) produced contraction (79.8 +/-7.1 g tension x g(-1)tissue) in the bladder rings that can be greatly reduced by prior addition of ATP or AP(4)A. Theophylline, a P(1)-purinoceptor antagonist, significantly reduced the contraction-induced by AP(4)A and did altered that produced by ATP in bladder rings. Atropine, a non-selective muscarinic receptor antagonist, or indomethacin, a cyclo-oxygenase inhibitor, significantly suppressed the contractions of the bladder rings to ATP or AP(4)A. Similarly, nifedipine, an l -type Ca(2+)channel blocker, significantly attenuate the contractions induced by ATP and AP(4)A in the isolated rat urinary bladder rings. In conclusion, the results of the present study show that ATP, AP(4)A, and EFS evoked contractions in the rat urinary bladder rings and that the contractions induced by AP(4)A was more potent than that produced by ATP. Furthermore, the contractions evoked by ATP or AP(4)A were Ca(2+)-dependent and mediated at least in part through one of the cyclo-oxygenase products. Also, the present results suggested the involvement of the P(1)-purinoceptor in mediating the contractions evoked by AP(4)A but not ATP in the bladder rings.
本研究旨在探讨三磷酸腺苷(ATP)和四磷酸二腺苷(AP(4)A)对离体大鼠膀胱环的作用及其可能的作用机制。ATP(0.1 - 1×10⁻³M)或AP(4)A(0.01 - 0.1×10⁻³M)能以浓度依赖的方式使离体膀胱环产生收缩。AP(4)A在膀胱环中诱导的收缩效力比ATP产生的收缩效力大约强十倍。在添加AP(4)A之前添加ATP,或者反之,会使膀胱组织对第二种激动剂脱敏,所产生的收缩大幅减弱。电场刺激(EFS,40V,0.5ms,2Hz)能使膀胱环产生收缩(79.8±7.1g张力×g⁻¹组织),而预先添加ATP或AP(4)A可使其大幅减弱。茶碱,一种P(1) - 嘌呤受体拮抗剂,能显著减弱AP(4)A诱导的收缩,但对ATP在膀胱环中产生的收缩无影响。阿托品,一种非选择性毒蕈碱受体拮抗剂,或吲哚美辛,一种环氧化酶抑制剂,能显著抑制膀胱环对ATP或AP(4)A的收缩。同样,硝苯地平,一种L型钙通道阻滞剂,能显著减弱ATP和AP(4)A在离体大鼠膀胱环中诱导的收缩。总之,本研究结果表明,ATP、AP(4)A和EFS能诱发大鼠膀胱环收缩,且AP(4)A诱导的收缩比ATP产生的收缩更有效。此外,ATP或AP(4)A诱发的收缩是钙依赖性的,且至少部分通过环氧化酶产物之一介导。而且,目前的结果提示P(1) - 嘌呤受体参与介导AP(4)A而非ATP在膀胱环中诱发的收缩。