Growth factor regulation of interleukin-1 beta-induced nitric oxide synthase and GTP: cyclohydrolase expression in cultured smooth muscle cells

Biochem Biophys Res Commun. 1993 Nov 15;196(3):1261-6. doi: 10.1006/bbrc.1993.2388.


Induction of NO synthase expression by interleukin-1 beta in cultured vascular smooth muscle cells from rat aortas was accompanied by simultaneous induction of GTP: cyclohydrolase I. This enzyme regulates the de novo synthesis pathway for tetrahydrobiopterin, an essential cofactor for the catalytic conversion of L-arginine to L-citrulline and NO by inducible NO synthase. Inhibition of GTP: cyclohydrolase attenuated NO production by interleukin-1 beta-stimulated smooth muscle cells. Peptide growth factors such as fibroblast growth factor, platelet-derived growth factor and transforming growth factor beta 1 and the protease thrombin have been shown to modulate the production NO by cytokine-treated smooth muscle cells. These peptide agonists also regulated the induction of NO synthase and GTP: cyclohydrolase mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / biosynthesis*
  • Animals
  • Aorta / drug effects
  • Aorta / enzymology
  • Blotting, Northern
  • Cells, Cultured
  • GTP Cyclohydrolase / biosynthesis*
  • Gene Expression / drug effects*
  • Growth Substances / pharmacology*
  • Interleukin-1 / pharmacology*
  • Kinetics
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology*
  • Nitric Oxide Synthase
  • Platelet-Derived Growth Factor / pharmacology
  • RNA, Messenger / biosynthesis
  • Rats
  • Transforming Growth Factor beta / pharmacology


  • Growth Substances
  • Interleukin-1
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • GTP Cyclohydrolase