C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells.
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.
Scios Nova, Mountain View, California 94043.
J G
JG
Porter
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R
Catalano
G
G
McEnroe
J A
JA
Lewicki
A A
AA
Protter
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D045283:Natriuretic Agents / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism
D045283:Natriuretic Agents; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016222:Fibroblast Growth Factor 2; D020098:Natriuretic Peptide, C-Type; D004247:DNA; D006162:Guanylate Cyclase