Iloprost-induced inhibition of proliferation of coronary artery smooth muscle cells is abolished by homologous desensitization.
In addition to inhibition of platelet function, prostacyclin and its stable analogues are reported to attenuate vascular smooth muscle cell proliferation. However, desensitization of prostacyclin responsiveness is a known phenomenon in platelets. In this study we investigated the time-dependent effects of the prostacyclin-mimetic iloprost and of PGE1, respectively, on PDGF-induced proliferation of cultured coronary artery smooth muscle cells. Proliferation, assessed by [3H]thymidine incorporation was markedly inhibited by coincubation with iloprost (100 nM) and PGE1 (100 nM) for 4 h. In contrast, addition of iloprost (100 nM) for 24 h did not decrease smooth muscle cell proliferation, whereas inhibition by PGE1 or by forskolin was not diminished. These results suggest a homologous desensitization of anti-mitogenic effects of iloprost in coronary artery smooth muscle cells, probably at receptor-level.
Grosser
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T
Institute für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
Bönisch
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D
Zucker
T P
TP
Schrör
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D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D013997:Time Factors
D010982:Platelet-Derived Growth Factor; D005576:Colforsin; D011451:Prostaglandin-Endoperoxide Synthases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000527:Alprostadil; D016285:Iloprost; D005459:Fluorides