Bradykinin and thrombin effects on polyphosphoinositide hydrolysis and prostacyclin production in endothelial cells.
Prostacyclin (PGI2) production by thrombin- and bradykinin-stimulated bovine aortic endothelial cells (BAEC) and human umbilical vein endothelial cells (HUVEC) was related to the receptor-linked activation of inositide hydrolysis. Bradykinin caused a rapid and transient 3-fold increase in the formation of inositol polyphosphates in BAEC. The increase in InsP3 reflected changes mainly in the Ins(1,4,5)P3 isomer. Thrombin was less effective than bradykinin in increasing InsP3 levels and appeared to only minimally stimulate the production of PGI2 in BAEC. In HUVEC, thrombin caused a 5-fold elevation of Ins(1,4,5)P3, closely related to a rise in PGI2 production. However, bradykinin did not affect inositol phosphates and PGI2 production in HUVEC. Other inositol phosphates were also assessed to obtain information on putative metabolism of Ins(1,4,5)P3. The present study supports the notion that formation of Ins(1,4,5)P3 is linked to an increase in PGI2 production in endothelial cells and furthermore provides evidence for a large degree of heterogeneity in the responses of BAEC and HUVEC to thrombin and bradykinin.
Bartha
K
K
Department of Inflammation Research, Troponwerke G.m.b.H. & Co. KG, Cologne, Federal Republic of Germany.
Müller-Peddinghaus
R
R
Van Rooijen
L A
LA
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D011460:Prostaglandins F / Q000032:analysis; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013917:Thrombin / Q000494:pharmacology*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011460:Prostaglandins F; D011464:Epoprostenol; D013917:Thrombin; D001920:Bradykinin; C100006:prostaglandin F1