PT  - JOURNAL ARTICLE
AU  - T Scott-Burden
AU  - E Elizondo
AU  - T Ge
AU  - C M Boulanger
AU  - P M Vanhoutte
TI  - Simultaneous activation of adenylyl cyclase and protein kinase C induces production of nitric oxide by vascular smooth muscle cells.
DP  - 1994 Aug 01
TA  - Molecular Pharmacology
PG  - 274--282
VI  - 46
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/46/2/274.short
4100  - http://molpharm.aspetjournals.org/content/46/2/274.full
SO  - Mol Pharmacol1994 Aug 01; 46
AB  - Rat aortic smooth muscle cells produced large quantities of nitric oxide (NO) after exposure to interleukin-1 beta, and this was depressed in the presence of the protein kinase C inhibitor bisindolylmaleimide. Intracellular cAMP levels were elevated mildly in cytokine-treated smooth muscle cells, and the presence of forskolin enhanced both the cAMP levels and NO production. Inhibition of GTP:cyclohydrolase I by 2,4-diamino-6-hydroxypyrimidine attenuated NO production by interleukin-1 beta-treated cells. GTP:cyclohydrolase is the regulatory enzyme for de novo tetrahydrobiopterin synthesis, and the latter is a required cofactor for NO synthase activity. Treatment of smooth muscle cells with forskolin induced GTP:cyclohydrolase mRNA expression, and simultaneous treatment of cells with forskolin and phorbol esters elicited NO production. Angiotensin II and arginine-vasopressin, acknowledged agonists for protein kinase C, elicited production of NO by forskolin-treated smooth muscle cells. These observations confirm the importance of GTP:cyclohydrolase activity for NO production by cultured smooth muscle cells and implicate both adenylyl cyclase and protein kinase C in this process.