Influence of indomethacin and aspirin on the contractile effects of prostaglandin F2alpha (PGF2alpha) at different Ca++ concentrations (experiments on guinea-pig ileum).
The direct effect of the prostaglandine synthetase inhibitors indomethacin and aspirin on the contractile effects of PGF2alpha at different Ca++ concentrations (1.5, 2.5 and 3.5 mM) in the Krebs solution was studied on isolated segments of guinea-pig ileum. It is established that after contact with indomethacin (3 X 10(-5) M) for 1-5 min the contractile effect of PGF2alpha (1 X 10(-7) M) decreases by 20-60%. Higher Ca++ content in the Krebs solution weakens the direct inhibitory effect of indomethacin. Unlike indomethacin, aspirin has no significant direct effect on prostaglandine contractions. Increase of Ca++ in the Krebs solution by 1 mM in itself does not change significantly the effect of PGF2alpha. Having in mind analogous results obtained in previous experiments with PGE1, it is concluded that indomethacin but not aspirin exercises a direct antagonistic action to the contractile effects of PGF2alpha and PGE1 on the guinea-pig ileum. The degree of this antagonistic action is in a definite dependence on the concentration of extracellular Ca++. Discussing the possible mechanisms of direct inhibitory action of indomethacin on the PGE1 and PGF2alpha effects on guinea-pig ileum, assumptions are made concerning the effect of indomethacin on the utilization of external Ca++ and the noncompetitive antagonistic action of indomethacin as a result of the interaction with allosteric (allotopic) sites of the prostaglandine receptor system.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D007082:Ileum; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D011460:Prostaglandins F / Q000494:pharmacology*; D013997:Time Factors
D002413:Cations, Divalent; D011460:Prostaglandins F; D001241:Aspirin; D002118:Calcium; D007213:Indomethacin