Inhibition of prostaglandin G/H synthase unveils a potent effect of platelet activating factor on the permeability of bovine aortic endothelial cells to albumin.
Platelet Activating Factor (PAF) is a very potent stimulant of various cell functions but little is known about the mechanisms responsible for its marked effect on endothelial permeability. An in vitro assay system was used to assess the direct effect of PAF on the permeability of a bovine aortic endothelial cell (BAEC) monolayer to albumin. PAF produced a small but not significant increase of the permeability of BAEC monolayer to albumin. However, pre-treatment of the monolayer with indomethacin (10 microM) resulted in a significant increase of BAEC permeability following PAF administration. This increase was concentration-dependent up to a maximal effect of 105% above basal value (for 0.1 microM PAF). Addition of the PAF antagonist SRI 63 441ZI (5 microM) abolished this effect. Exogenous administration of PGE2 (10(-7) M) inhibited the effect of PAF on the BAEC permeability suggesting that prostaglandins synthesized by the endothelium behave as a negative autoregulatory factor. Compound SRI 63 441ZI also partially inhibited bradykinin-induced permeability to albumin but did not significantly modify the activity of thrombin. These findings show that PAF can increase endothelial permeability to albumin when the synthesis of prostaglandins is inhibited. Our results also show that PAF might have an autocrine activity by mediating part of BK-induced permeability.
Farmer
Pierre J
PJ
lnstitute of Pharmacology of Sherbrooke, Medical School, Université de Sherbrooke, Sherbrooke, PQ, Canada.
Girardot
Daphné
D
Lepage
Andrée
A
Regoli
Domenico
D
Sirois
Pierre
P
D000818:Animals; D001011:Aorta; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D016861:Cyclooxygenase Inhibitors; D010972:Platelet Activating Factor; D012710:Serum Albumin, Bovine; D011451:Prostaglandin-Endoperoxide Synthases