Comparative study of the contractile activity evoked by ATP and diadenosine tetraphosphate in isolated rat urinary...

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.