Dual inhibition of cyclooxygenase and lipoxygenase enzymes by human cerebrospinal fluid.
Thromboxane A2 (TXA2) formed in damaged brain tissue and after thromboembolism and subarachnoid haemorrhage is responsible for cerebral vasospasm. In the present study, we examined the effect of human cerebrospinal fluid (CSF) on the production of thromboxane-A2 (TXA2) and 12-hydroxy-eicosatetraenoic acid (12-HETE) by human blood platelets. CSF was drawn by lumbar puncture from normal healthy volunteers (n = 17) and samples judged to be normal after routine examination in the clinical laboratories and were used fresh. We found that CSF inhibited the production of TXA2 and 12-HETE by blood platelets incubated with C14 labelled arachidonic acid (AA) in a concentration-related manner. Further biochemical analysis using proteolytic enzymes, gel filtration and membrane partition chromatography showed that the inhibitory activity was peptidic in nature and associated with a peptide of low molecular weight (1,400 Da). This study is the first to demonstrate that human CSF contains a dual inhibitor of cyclooxygenase (COX) and lipoxygenase enzymes in CSF.
Saeed
Sheikh Arshad
SA
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. sarshadsaeed@yahoo.com
Shad
Kaneez Fatima
KF
Simjee
Shabana Usman
SU
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000328:Adult; D001792:Blood Platelets; D002555:Cerebrospinal Fluid / Q000187:drug effects*; D002933:Cineradiography; D006801:Humans; D008084:Lipoxygenase / Q000494:pharmacology*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism
D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases