title: 2-Phenyl-4-quinolone prevents serotonin-induced increases in endothelial permeability to albumin.
abstract: To investigate the role of 2-phenyl-4-quinolone in enhancing endothelial monolayer paracellular barrier function and preventing the disturbance of paracellular barrier function by vasoactive agents, the study examined the effect of 2-phenyl-4-quinolone on serotonin-mediated macromolecule transfer and microfilament changes in cultured rat heart endothelial cells. Serotonin-treated endothelial cells induced concentration-dependent increases in the passage of Evans blue dye-bound bovine serum albumin. Incubation of the endothelial monolayers with 2-phenyl-4-quinolone antagonized serotonin- and cytochalasin B-induced macromolecular permeability. 2-Phenyl-4-quinolone also opposed the effect of serotonin or cytochalasin B on the distribution and quantity of actin filaments in the endothelial cytoskeleton. Furthermore, 2-phenyl-4-quinolone alone led to an apparent quantitative increase in F actin fluorescence in endothelial cells. The addition of 10(-7) M 2-phenyl-4-quinolone had an effect on serotonin-induced changes in the myosin and distribution of myosin were comparable to that on serotonin monolayers. In conclusion, 2-phenyl-4-quinolone attenuated the serotonin-induced permeability of rat heart endothelial cells and this was associated with stabilization of F actin microfilaments and changes in the myosin organization. This result suggests that influences on cytoskeletal assembly may be involved in this process.
authors.affiliation: School of Pharmacy, China Medical College, Taichung, Taiwan.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Lee
authors.forename: W C
authors.initials: WC
authors.lastname: Lin
authors.forename: F T
authors.initials: FT
authors.lastname: Yeh
authors.forename: C H
authors.initials: CH
authors.lastname: Wu
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006321:Heart / Q000187:drug effects; D009218:Myosins / Q000378:metabolism; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000199:Actins; D002316:Cardiotonic Agents; D015363:Quinolones; D012702:Serotonin Antagonists; D012709:Serum Albumin; C084179:2-phenyl-4-oxohydroquinoline; D012701:Serotonin; D003571:Cytochalasin B; D000242:Cyclic AMP; D009218:Myosins