title: Superoxide anion stress attenuates the contractile response of the Guinea pig vas deferens to ATP and diadenosine tetraphosphate. Possible effect on calcium dysregulation.
abstract: Induction of endogenous superoxide anion stress by the use of the superoxide dismutase inhibitor diethylthiocarbamate (DETCA; 10 mmol/l) produced a potent inhibition of the ATP (0.3-10 mmol/l) and diadenosine tetraphosphate (AP(4)A) contractile activity in the isolated vas deferens by 29-92 and 24-90%, respectively. Pyrogallol (0.1 mmol/l), the exogenous superoxide anion generator, produced a significant inhibition on the contractile activity of the vas deferens induced by ATP and AP(4)A by 33-89 and 25-82%, respectively. DETCA (10 mmol/l) and pyrogallol (0.1 mmol/l) attenuated the contractile response of isolated guinea pig vas deferens strips to the selective P2X agonist alpha,beta-methyleneATP (alpha,beta-meATP; 50 micromol/l) by 25 and 47%, respectively. In Ca(2+)-free high-K(+) (80 mmol/l) Krebs solution, pyrogallol and DETCA produced inhibition of the contractile response to alpha,beta-meATP (50 micromol/l) in similar way to that in normal Krebs solution. The further addition of CaCl(2) (1 mmol/l) abolished the inhibitory effects exerted by pyrogallol and DETCA. The control contractile response to alpha,beta-meATP (50 micromol/l) was not affected in Ca(2+)-free high-K(+) (80 mmol/l) Krebs solution. It may be concluded that superoxide anion stress produces a significant inhibitory effect on both mono- and di-nucleotide purinergic contraction of the vas deferens. Superoxide anion appears to interrupt the P2X(1)-mediated transduction cascade at some step(s) of intracellular calcium handling.
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mahmood B
authors.initials: MB
authors.lastname: Al-Rawi
authors.forename: Abdulaziz M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Khattab
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011748:Pyrogallol / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015226:Dinucleoside Phosphates; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D011748:Pyrogallol; D013481:Superoxides; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium