Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in the rats: role of superoxide anion and urothelium.
Both ATP and diadenosine tetraphosphate (AP(4)A) produced a dose-dependent contraction of rat isolated urinary bladder rings. The AP(4)A dose-response curve was to the left of that of ATP, and the maximum response was greater than that produced by ATP. Mechanical removal of the urothelium increased the contractile response to ATP by between 53% and 71%, and that to AP(4)A by 42% (at highest AP(4)A concentration) to 68% at lower concentration. Inhibition of Cu/Zn superoxide dismutase with diethylthiocarbamate (DETCA, 5 mm) significantly reduced the ATP-evoked contraction by 31% (at high ATP concentration) to 40% at low ATP concentration. Similarly, the AP(4)A-induced contractions were significantly decreased by 27% at low AP(4)A level to 38% at higher concentrations. Induction of exogenous superoxide anion stress by the use of the superoxide anion generator, pyrogallol (0.5 mm), significantly decreased both ATP- and AP(4)A-induced contractions of the rat urinary bladder over the whole dose range. Contractile responses to ATP decreased by 36-40%, and those to AP(4)A by 44-49%. In conclusion, the urinary bladder urothelium exerts an inhibitory control over the purinergic contractility produced by adenine mononucleotides and dinucleotides. Superoxide anion stress, whether endogenous or exogenous, attenuates the ATP-induced as well as AP(4)A-induced contractility.
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
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Khattab
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Al-Hrasen
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D015226:Dinucleoside Phosphates; D004791:Enzyme Inhibitors; D011748:Pyrogallol; D013481:Superoxides; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase