AJP - Cell Physiology, Vol 258, Issue 3 C408-C415, Copyright © 1990 by American Physiological Society
Growth factor activity of endothelin on vascular smooth muscle
A. Bobik, A. Grooms, J. A. Millar, A. Mitchell and S. Grinpukel
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
Endothelin is a novel peptide secreted by endothelial cells, the
vasoconstrictor effects of which appear dependent on the activation of
phospholipase C. We examined in tissue culture its potential as a growth
factor for vascular smooth muscle. In quiescent cultures of rat aortic
smooth muscle cells, endothelin rapidly elevated levels of c-fos and c-myc
mRNA. Peak effects on c-fos mRNA occurred between 15 and 30 min and were
completely gone after 2 h. The elevation in c-fos mRNA was, in part,
dependent on protein kinase C, since phorbol myristate acetate (PMA) also
elevated c-fos mRNA and further increased c-fos mRNA expression by
endothelin, but the effects were not additive. Furthermore, the
endothelin-induced elevation in c-fos mRNA was attenuated but not abolished
in protein kinase C-depleted cells. Maximum levels of c-myc mRNA occurred
between 15 and 30 min after exposing the cells to endothelin and persisted
for at least 6 h. The effects of simultaneous addition of endothelin and
PMA on c-myc mRNA levels were essentially similar to those observed with
c-fos mRNA. [3H]thymidine incorporation into DNA occurred 8 h after
exposing the cells to endothelin. The mitogenic effect of endothelin was
smaller than that observed with either fetal calf serum or epidermal growth
factor and was dependent on both pertussis toxin-insensitive and -sensitive
pathways. Sensitivity to the latter pathway did not appear dependent on
attenuation of phospholipase C activity, since neither peak intracellular
calcium concentrations nor c-fos mRNA levels were reduced in pertussis
toxin-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
