Mechanism of ionophore A23187 induction of plasma protein leakage and of its inhibition by indomethacin |
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Authors: | G Thomas |
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Institution: | Department of Pharmacology, Merck Institute for Therapeutic Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486, U.S.A. |
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Abstract: | 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. |
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Keywords: | Dopamine agonists Autoreceptor Domperidone 3-PPP |
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