Permeability of endothelial monolayers to albumin is increased by bradykinin and inhibited by prostaglandins.
Using monolayers of bovine aortic endothelial cells (BAEC) in modified Boyden chambers, we examined the role of prostaglandins (PGs) in the bradykinin (BK)-induced increase of albumin permeability. BK induced a concentration-dependent increase of the permeability of BAEC, which reached 49.9 +/- 1% at the concentration of 10(-8) M. Two inhibitors of the prostaglandin G/H synthase, indomethacin (2.88 microM) and ibuprofen (10 microM), potentiated BK-induced permeability 1.8- and 3.9-fold, respectively. Exogenously administered PGE2 and iloprost, a stable analog of prostacyclin, attenuated the effect of BK in a concentration-dependent manner. Butaprost equally reduced the effect of BK, suggesting the participation of the EP2 receptor in this phenomenon. However, the EP4-selective antagonist AH-23848 did not significantly inhibit the protective effect of PGE2. The inhibitory effect of PGE2 was reversed by the adenylate cyclase inhibitor MDL-12330A (10 microM). These results suggest that BK-induced increase of permeability of BAEC monolayer to (125)I-labeled albumin is negatively regulated by PGs. This postulated autocrine activity of PGs may involve an increase in the intracellular level of cAMP.
Institut de Pharmacologie de Sherbrooke, Medical School, University of Sherbrooke, Sherbrooke, Quebec, Canada J1H 5N4.
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Farmer
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Bernier
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Lepage
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Guillemette
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Regoli
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Sirois
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016285:Iloprost / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D012709:Serum Albumin; D000242:Cyclic AMP; D000527:Alprostadil; C048491:butaprost; D016285:Iloprost; D015232:Dinoprostone; D000420:Albuterol; D001920:Bradykinin