Angiotensin peptide regulation of bovine brain microvessel endothelial cell monolayer permeability.
The passage of fluid-phase endocytosis markers--Lucifer yellow and a fluorescein isothiocyanate-conjugated dextran--across confluent primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers was characterized in the presence of angiotensin II (Ang II) peptides. Exposure to nanomolar concentrations of saralasin, an Ang II agonist, attenuated the passage of the fluorophores across the monolayers by 50-75%. In contrast, exposure to sarathrin, an Ang II antagonist, had no effect on passage of the fluorophores across the BMEC monolayers. Sarathrin, however, did inhibit the saralasin-induced reduction in transendothelial monolayer permeability and suggested specific Ang II binding site mediation. Other experiments performed suggest that saralasin-induced changes in BMEC monolayer permeability can be blocked by pretreatment with inhibitors of prostaglandin synthesis and that substantial saralasin-induced changes in BMEC monolayer permeability occurred only following exposure on the apical side of the endothelial cells. Results were consistent with previous studies demonstrating the existence of specific Ang II binding sites on BMECs and Ang II regulation of fluid-phase endocytosis. In addition, these studies support the role of angiotensin peptides in modulating permeability properties of the blood-brain barrier.
Guillot
F L
FL
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence 66045.
Audus
K L
KL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003911:Dextrans / Q000493:pharmacokinetics; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000493:pharmacokinetics; D012504:Saralasin / Q000494:pharmacology
D003911:Dextrans; D005452:Fluoresceins; D007546:Isoquinolines; C015219:fluorescein isothiocyanate dextran; C017475:lucifer yellow; D012504:Saralasin; D016650:Fluorescein-5-isothiocyanate