Blocking of histamine release from human basophils in vitro by the ATPase inhibitor, ethacrynic acid.
Ethacrynic acid, a known inhibitor of both Na+--K+ and Mg2+-activated ATPases, effectively inhibits histamine release from antigen-challenged human basophils in vitro. Ouabain, an inhibitor specific for Na+--K+-activated ATPases, shows no effect upon the quantity of histamine released from the antigen-challenged basophils. Ethacrynic acid also effectively inhibits Ca2+--ionophore A23187-induced release, implying it inhibits the Ca2+-dependent secretory stage of the histamine-release process. Inhibition of ATPases and histamine release by ethacrynic acid both require the presence of the olefinic bond in the ethacrynic-acid molecule. Possible utilization of analogues of ethacrynic acid as anti-allergic drugs and as a device to investigate the ATPase system of histamine-releasing cells is suggested.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001491:Basophils / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004976:Ethacrynic Acid / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D013438:Sulfhydryl Compounds; D007073:Immunoglobulin E; D000001:Calcimycin; D010042:Ouabain; D000251:Adenosine Triphosphatases; D003545:Cysteine; D004976:Ethacrynic Acid