SK&F 96365 inhibits histamine-induced formation of endothelium-derived relaxing factor in human endothelial cells. |
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Authors: | W F Graier K Groschner K Schmidt W R Kukovetz |
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Institution: | Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universit?t Graz, Austria. |
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Abstract: | Formation of endothelium-derived relaxing factor (EDRF) strictly correlates with the intracellular free Ca2+ (Ca2+]i) concentration. We now demonstrate that the histamine-induced rise in Ca2+]i of human umbilical vein endothelial cells is mostly due to activation of a membrane current which allows Ca2+ entry. This membrane current is sensitive to the novel inhibitor of agonist-induced Ca2+ entry, SK&F 96365, which blocked the histamine-induced sustained rise in Ca2+]i, as well as 45Ca2+ uptake and membrane currents. Inhibition of the above cellular responses to histamine was accompanied by a considerable reduction of EDRF formation and release. Thus biosynthesis and release of EDRF from human umbilical vein endothelial cells significantly depend on agonist-induced Ca2+ entry involving receptor-operated Ca(2+)-permeable channels which can be blocked by SK&F 96365. |
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