title: Iloprost-induced inhibition of proliferation of coronary artery smooth muscle cells is abolished by homologous desensitization.
abstract: 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.
authors.affiliation: Institute für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
authors.forename: T
authors.initials: T
authors.lastname: Grosser
authors.forename: D
authors.initials: D
authors.lastname: Bönisch
authors.forename: T P
authors.initials: TP
authors.lastname: Zucker
authors.forename: K
authors.initials: K
authors.lastname: Schrör
mesh_terms: 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
chemical_list: D010982:Platelet-Derived Growth Factor; D005576:Colforsin; D011451:Prostaglandin-Endoperoxide Synthases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000527:Alprostadil; D016285:Iloprost; D005459:Fluorides