Source:http://linkedlifedata.com/resource/pubmed/id/21117404
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
2010-12-1
|
pubmed:abstractText |
Protein kinase G (PKG) is abundant in neonatal ovine lung microvascular endothelial cells (LMVECs) but its various functions are not known. To test the hypothesis that PKG plays a role in feedback regulation of nitric oxide (NO) synthesis, we studied the effects of modulators of PKG signaling on real time NO release from LMVECs microcultures in 96-well clusters. We used 0.5 - 2.43 microM DAF FM and DAF-FM diacetate to measure amount of NO present in the cells and in the cell bathing medium. We found a dose-response relationship between 8-Br-cGMP (0.02 - 2 microM), a stimulator of PKG activity, and inhibition of basal NO production. The time-course of the effect of 2 microM 8-Br-cGMP on NO production exhibited a parallel shift downwards in the presence of PKG receptor inhibitor, 100 ng/ml DT-2, indicating that 8-Br-cGMP acts through PKG to inhibit NOS. PKG also decreased stimulated NO production: acetylcholine produced raw fluorescence of 59999 +/- 702 and in the presence of 1 mM 8-Br-cGMP the value was 20645 +/- 292 (p < 0.0001) while carbachol produced raw fluorescence of 60600 +/- 890 and in the presence of 1 mM 8-Br-cGMP was 30442 +/- 2000 (p < 0.01). The PKG inhibitor 125 nM guanosine 3'-5'-cyclic-monophosphorothionate-8-Br-Rp isomer increased basal NO production (p < 0.01). NO synthase inhibitor, L-NNA reversed this effect (p < 0.05) as well as that of another PKG inhibitor 25 microM Rp-8-Br-PET-cGMPS but enhanced the effect of 25 microM 8-Br-cGMP. Both basal and stimulated NO production is regulated by the downstream activation of PKG by NO-induced 8-Br-cGMP production in endothelial cells.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-bromo-beta-phenylethenoguanosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jun
|
pubmed:issn |
0309-3913
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
39
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
89-98
|
pubmed:meshHeading |
pubmed-meshheading:21117404-Animals,
pubmed-meshheading:21117404-Cyclic GMP,
pubmed-meshheading:21117404-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:21117404-Endothelial Cells,
pubmed-meshheading:21117404-Lung,
pubmed-meshheading:21117404-Nitric Oxide,
pubmed-meshheading:21117404-Nitric Oxide Synthase Type III,
pubmed-meshheading:21117404-Sensitivity and Specificity,
pubmed-meshheading:21117404-Sheep
|
pubmed:year |
2010
|
pubmed:articleTitle |
Protein kinase G inhibits basal and stimulated nitric oxide synthase activity in neonatal ovine lung microvascular endothelial cells.
|
pubmed:affiliation |
Department of Pharmacology, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria. theresaadebola@yahoo.com
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
|