Inhibition of prostacyclin formation by cyclosporin is not due to reduced availability of arachidonic acid in membrane phospholipids of cultured human endothelial cells.
Our studies have shown that CS inhibits PGI2 production in HUVEC, that this inhibition is not overcome when exogenous AA is supplied, that the inhibitory action of CS is proximal to PGI2 synthetase and finally that there is abundant free AA available in membrane phospholipids of CS treated HUVEC [4,5]. In conclusion, CS does not appear to inhibit PGI2 synthesis by reducing the availability of free AA in the endothelial cell membrane. Although CS appears to inhibit cyclo-oxygenase, we can not exclude an additional effect on acyltransferase.
Brown
Z
Z
Department of Renal Medicine, Institute of Urology, St Paul's Hospital, London, U.K.
Neild
G H
GH
Lewis
G P
GP
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology*; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*
D001095:Arachidonic Acids; D003524:Cyclosporins; D008563:Membrane Lipids; D010743:Phospholipids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol