Mechanism of ionophore A23187 induction of plasma protein leakage and of its inhibition by indomethacin.
Calcium ionophore A23187 produced a dose-dependent increase in plasma protein leakage on intradermal injection in rats. Studies with mepyramine and cyproheptadine indicated that histamine and 5-hydroxytryptamine (5-HT) partially contribute to the ionophore action and experiments with compound 48/80 supported these findings. Depletion of plasma kininogen levels with cellulose sulphate administered indomethacin inhibited the ionophore response in a dose-dependent manner. The inhibition was not reversed by intradermally injected prostaglandin E2 (PGE2) in doses up to 50 ng/site, suggesting that PGE2 also may not be an important mediator. It is proposed that the ionophore produces plasma protein leakage by an indirect (through histamine and 5-HT release) and a direct action on vascular endothelial cells and that indomethacin antagonises both actions by inhibiting calcium transport processes.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology*; D003533:Cyproheptadine / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D003911:Dextrans; D011458:Prostaglandins E; D003533:Cyproheptadine; D000001:Calcimycin; D011738:Pyrilamine; D015232:Dinoprostone; D007213:Indomethacin