Platelet activating factor production in bovine cerebral microvascular endothelial cells and its drug inhibition.
The production of platelet activating factor (PAF) in bovine cerebral microvascular endothelial cells (CME cells) and the effects of tetrandrine (Tet) and dauricine (Dau) on the PAF production were investigated. PAF was determined by the aggregation of washed rabbit platelets. The results showed that the CME cells produced PAF 5.93 ng/8.5x 10(5) cells under the calcimycin 2.5 mumol.L-1 stimulation. Tet and Dau 1, 10, and 100 mumol.L-1 inhibited the production of PAF by 18.2%, 51.8%, 56.8%, and 26.3%, 63.3%, 65.9%, respectively. Tet concentration-dependently inhibited the PAF 9.1 nmol.L-1 induced washed rabbit platelets aggregation with the IC50 of 3.05 mumol.L-1 (95% confidence limits: 0.59-15.86 mumol.L-1). The binding of [3H]triazolodiazepine to the CME cells was partially displaced by Tet 0.02-33.00 mumol.L-1. It is suggested that the cerebrovascular system produces PAF at the pathological conditions and the inhibition of Tet and Dau.
Sun
D X
DX
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
Huang
T G
TG
Zeng
G Q
GQ
Rui
Y C
YC
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D001921:Brain / Q000098:blood supply*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008833:Microcirculation / Q000166:cytology; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D044005:Tetrahydroisoquinolines
D000470:Alkaloids; D044182:Benzylisoquinolines; D007546:Isoquinolines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D044005:Tetrahydroisoquinolines; C009438:tetrandrine; D000001:Calcimycin; C035934:dauricine