Contributions of NO synthase and heme oxygenase to cGMP formation by cytokine and hemin treated brain capillary endothelial cells.
Two mechanisms contribute to cGMP formation by soluble guanylyl cyclase (i) NO production by NO synthase and (ii) CO production by heme oxygenase. We analyze here the contributions of these two pathways to IL1, TNF, lipopolysaccharide and hemin treated brain capillary endothelial cells. Cytokines and LPS induced cGMP formation in manners that were completely prevented by LY 83,583, methylene blue and by cyclosporin A. They were partially inhibited by inhibitor of NO synthase. Cyclosporin A acts by a posttranscriptional mechanism. Cells constitutively expressed mRNAs for heme oxygenase-1. Expression was enhanced by hemin but not by IL1 or lipopolysaccharide. Induction of heme oxygenase-1 and its inhibition by Sn protoporphyrin IX had no effect on cGMP levels.
Vigne
P
P
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Université de Nice-Sophia, Valbonne, France.
Feolde
E
E
Ladoux
A
A
Duval
D
D
Frelin
C
C
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology*; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006427:Hemin; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP