Thromboxane A(2) induces cell signaling but requires platelet-derived growth factor to act as a mitogen

This study investigates thromboxane A(2)-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 mu M) 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-oxabicyc[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 A, 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).