Inhibition by prostacyclin and carbacyclins of endothelin-induced DNA synthesis in cultured vascular smooth muscle cells.
Effects of prostacyclin and carbacyclins on endothelin-induced DNA synthesis were investigated in vascular smooth muscle cells. DNA synthesis was estimated by [3H]thymidine incorporation. Five carbacyclins used in this report were 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo [3.3.0]oct-2-en-3-yl) pentanoic acid (TEI-7165), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl]bicyclo[3.3.0]oct-2-en-3- yl]pentanoate (TEI-9090), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1-nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)penta noic acid (TEI-9063), methyl 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(3S, 5S)-3-hydroxy-5-methyl-1- nonenyl]bicyclo[3.3.0]oct-2-en-3-yl)pentanoate (TEI-1324), 5-[(1S, 5S, 6R, 7R)-7-hydroxy-6-[(E)-(S)-4-hydroxy-4-methyl-1- octenyl]bicyclo[3.3.0]oct-2-en-3-yl] pentanoic acid (TEI-3356). Prostacyclin and the carbacyclins inhibited the endothelin-induced DNA synthesis within the nanomolar range. These results suggest that prostacyclin and carbacyclins are possibly effective in inhibiting the proliferation of vascular smooth muscle cells under some situations in vivo.
Nakaki
T
T
Department of Pharmacology, Keio University School of Medicine, Tokyo, Japan.
Ohta
M
M
Kato
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D003864:Depression, Chemical; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins; C074592:TEI 1324; C057340:17,20-dimethylisocarbacyclin; C074591:TEI 3356; C052840:TEI 9090; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol