AJP - Cell Physiology, Vol 262, Issue 4 C927-C933, Copyright © 1992 by American Physiological Society
Growth factors downregulate vascular smooth muscle thromboxane receptors independent of cell growth
G. W. Dorn 2nd and M. W. Becker
Department of Medicine/Cardiology, University of Cincinnati College of Medicine, Ohio 45267.
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-(1 alpha 2 beta(5Z),3 alpha(1E,3S),4
alpha)]-7-[3-(3-hydroxy-4-p-
iodophenoxy-1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-hep tenoic 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.
