Agonist specific desensitization of leukotriene C sub(4)-stimulated PGI sub(2) biosynthesis in human endothelial cells

Leukotriene C sub(4) (LTC sub(4)) and, to a lesser extent, leukotriene D sub(4) (LTD sub(4)) concentration dependently stimulate prostacyclin (PGI sub(2)) biosynthesis in cultured human umbilical vein endothelial cells. PGI sub(2) biosynthesis was quantitated by radioimmunoassay and its structure confirmed by gas chromatography/mass spectrometry. Preincubation of endothelial cells with LTC sub(4) resulted in desensitizaiton to subsequent LTC sub(4) stimulation. However, PGI sub(2) biosynthesis in response to thrombin, PGH sub(2) and arachidonic acid was not inhibited by preincubation with LTC sub(4). The C-6-sulfidopeptide leukotriene receptor level antagonist FPL-55712 attenuates LTC sub(4), but not thrombin-stimulated PGI sub(2) biosynthesis. These data suggest that human umbilical vein endothelial cells have a C-6-sulfidopeptide leukotriene receptor, and that stimulation of this receptor results in PGI sub(2) biosynthesis.