Up-regulation of endothelial nitric oxide synthase expression by cyclic guanosine 3',5'-monophosphate.
In this study, the role of cyclic GMP, the end product of the NO-cyclic GMP signalling pathway, in the regulation of ecNOS was investigated. Bovine pulmonary endothelial cells were exposed to 8-bromo-cyclic GMP and its effect on NO production, ecNOS protein, and mRNA levels was analyzed. Endothelial cells on exposure to 8-bromo-cyclic GMP produced significantly increased amounts of NO, detected as increased cyclic GMP in cocultures with vascular smooth muscle cells both under basal conditions and with agonist stimulation. 8-Bromo-cyclic GMP significantly increased the ecNOS protein and mRNA levels as detected on Western and Northern blots respectively. This 8-bromo-cyclic GMP mediated increase of NO production, ecNOS protein and mRNA levels suggests that cyclic GMP up-regulates the expression of ecNOS. Thus, there may be an intercellular feedback mechanism involved at the molecular level in the expression of the NO-cyclic GMP signalling pathway in blood vessels.
Ravichandran
L V
LV
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Johns
R A
RA
D000818:Animals; D002417:Cattle; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D005246:Feedback; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D012333:RNA, Messenger; C016276:8-bromocyclic GMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP