Effects of OP-41483.alpha-CD, a stable prostacyclin analog, on cultured endothelial cell dysfunction caused by 15(S)-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) in vitro.
We studied the effect of OP-41483.alpha-CD, a stable prostacyclin analog, on, 15-HPETE induced bovine endothelial cell dysfunction, which was assessed by measuring a number of endothelial cells attached to plastic plates. 15-HPETE decreased the number of attached endothelial cells in a concentration- and time-dependent manner. OP-41483.alpha-CD and PGI2 significantly inhibited 15-HPETE induced dysfunction of the cells at a concentration of more than 10(-9)M. Besides, DDA (10(-6) - 10(-4)M) an adenylate cyclase inhibitor, diminished the inhibitory effect of OP-41483.alpha-CD on 15-HPETE induced cell dysfunction in a concentration-dependent manner. Furthermore, OP-41483.alpha-CD increased cAMP levels in the endothelial cells in the range of 10(-10) to 10(-8)M in a dose-dependent manner. These data suggest that OP-41483.alpha-CD could exert an inhibitory action on 15-HPETE induced endothelial cell dysfunction via partly increasing its effect on the intracellular cAMP level.
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
R
R
Matsumoto
M
M
Naka
N
N
Omawari
B
B
Fujitani
H
H
Aishita
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003505:Cyclodextrins / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D015289:Leukotrienes; D008054:Lipid Peroxides; D014662:Vasoconstrictor Agents; D047391:alpha-Cyclodextrins; C043214:prostaglandin E1-alpha-cyclodextrin; C051518:OP 41483-alpha-cyclodextrin; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil