Inhibitory effect of 2-phenyl-4-quinolone on serotonin-mediated changes in the morphology and permeability of endothelial monolayers.
The integrity of endothelial cell monolayers, a critical requirement for barrier maintenance, is needed for the prevention of edema formation. To investigate the mechanisms by which 2-phenyl-4-quinolone (YT-1) provided protection against serotonin-induced exudation, rat heart endothelial cell cultures were used. In this study, serotonin and phorbol myristate acetate (PMA) caused endothelial cells to became permeable to macromolecules by causing cell contraction and intercellular gap formation. These responses were attenuated by staurosporine, a protein kinase C inhibitor. Further experiments showed that YT-1 (1) did not alter serotonin-mediated early signal events such as protein kinase C activation, (2) protected against serotonin-induced endothelial barrier dysfunction by increasing intracellular cAMP levels, (3) played a role in regulating adenylate cyclase activity, (4) reversed serotonin-induced permeability to macromolecules, an effect which did not correlate with intracellular cGMP concentrations. This study demonstrates a possible mechanism by which YT-1 protects endothelial function and preserves the microvasculature from pharmacologic injury by vasoactive agents.
Lee
H Z
HZ
Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D012709:Serum Albumin / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015363:Quinolones; D012709:Serum Albumin; C084179:2-phenyl-4-oxohydroquinoline; D009599:Nitroprusside; D005576:Colforsin; D012701:Serotonin; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine