AJP - Cell Physiology, Vol 263, Issue 5 C1001-C1006, Copyright © 1992 by American Physiological Society
C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells
J. G. Porter, R. Catalano, G. McEnroe, J. A. Lewicki and A. A. Protter
Scios Nova, Mountain View, California 94043.
We have examined the ability of C-type natriuretic peptide (CNP) to
interact with guanylate cyclase-coupled natriuretic peptide receptors by
measuring its ability to stimulate intracellular guanosine 3',5'-cyclic
monophosphate (cGMP) accumulation in cultured bovine aortic endothelial
(BAE) and bovine aortic smooth muscle (BASM) cells. Our experiments
indicate that CNP is unable to stimulate the production of cGMP in BAE
cells, whereas both atrial natriuretic peptide (ANP) and brain natriuretic
peptide (BNP) markedly elevate cGMP levels in these cells (ANP = BNP
>> CNP). In contrast, CNP is the most effective of the three peptides
with respect to the stimulation of cGMP levels in BASM cells, fetal human
vascular smooth muscle cells, and rat A10 cells (CNP >> ANP >
BNP), with the maximal level of stimulation being approximately 5- to
10-fold over that observed for ANP. We have also shown that CNP is able to
inhibit serum- and growth factor-induced DNA synthesis in BASM cells. Low
concentrations of CNP (20 x 10(-9) M) inhibit up to 80% of the
[3H]-thymidine incorporation induced by basic fibroblast growth factor,
platelet derived growth factor, epidermal growth factor (EGF), and heparin
binding EGF-like growth factor. These data indicate that, although CNP has
been detected only in the central nervous system and not in the
circulation, it may possess multiple effects on vascular tissue.
