Growth factors downregulate vascular smooth muscle thromboxane receptors independent of cell growth

Growth factors, in addition to being mitogenic, may modulate vascular smooth muscle differentiation. We tested whether serum or defined growth factors could regulate thromboxane A₂ (TxA₂) receptors in cultured rabbit aorta smooth muscle cells. Fetal bovine serum (10%) stimulated cell proliferation and DNA synthesis in subconfluent cell cultures. Binding of the thromboxane A₂ agonist [1S-(1α2β(5Z),3α(1E,3S),4α)]-7-[3-(3-hydroxy-4-p- iodophenoxy-1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid showed a 41% decrease in TxA₂ receptors in cells treated with 10% serum compared with serum-deprived (0.1%) controls. Receptor downregulation by serum was gradually reversible upon serum withdrawal. Compared with serum- deprived cells, those exposed to 10% serum also had diminished TxA₂- stimulated phosphatidylinositol hydrolysis. Regulatory actions of serum on TxA₂ receptors were distinguished from mitogenic effects with heparin, which prevented cell growth but did not inhibit serum-induced downregulation of TxA₂ receptors. Furthermore, low concentrations of platelet-derived growth factor and basic fibroblast growth factor decreased TxA₂ receptors without stimulating cell proliferation or DNA synthesis. These observations describe a previously unrecognized regulatory action of growth factors on a vascular smooth muscle vasoconstrictor receptor, an action which is independent of effects on cell proliferation or DNA synthesis.