Thromboxane A2 induces cell signaling but requires platelet-derived growth factor to act as a mitogen.
This study investigates thromboxane A2-induced cell signaling and mitogenesis of bovine coronary artery smooth muscle cells. The thromboxane mimetic U 46619 [(15S)-hydroxy-11,9-(epoxymethano) prosta-5Z,13E-dienoic acid] (10 microM) stimulated [Ca2+]i signals, phosphorylation of MAP kinase (mitogen-activated protein kinase), and expression of c-fos mRNA in smooth muscle cells. In contrast, no stimulation of DNA synthesis or cell proliferation by U 46619 was observed. However, platelet-derived growth factor-BB (20 ng/ml)-induced mitogenesis was potentiated by U 46619. Similar results were obtained with I-BOP [1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo [2.2.1] heptan-2-yl]-5-heptenoic acid]. These potentiating effects were abrogated by a specific thromboxane receptor antagonist, suggesting that the potentiation of platelet-derived growth factor-BB-induced smooth muscle cell mitogenesis by U 46619 and I-BOP was mediated by thromboxane receptors. It is concluded that thromboxane A2 generated by blood platelets at the site of vessel injury induces cell signaling in smooth muscle cells but acts as a mitogen only in the presence of growth factor(s).
Grosser
T
T
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Zucker
T P
TP
Weber
A A
AA
Schulte
K
K
Sachinidis
A
A
Vetter
H
H
Schrör
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D016760:Proto-Oncogene Proteins c-fos; D014662:Vasoconstrictor Agents; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D004247:DNA; D002118:Calcium