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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1997-2-3
|
| pubmed:abstractText |
Dopamine decreases tubular sodium reabsorption in part by inhibition of Na+,K(+)-ATPase activity in renal proximal tubules. The signaling mechanism involved in dopamine-mediated inhibition of Na+,K(+)-ATPase is known to be defective in spontaneously hypertensive animals. The present study was designed to evaluate the role of phospholipase A2 (PLA2) and its metabolic pathway in dopamine-induced inhibition of Na+,K(+)-ATPase in renal proximal tubules from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Renal proximal tubular suspensions were prepared and Na+,K(+)-ATPase activity was measured as ouabain-sensitive adenosine triphosphate hydrolysis. Dopamine inhibited Na+,K(+)-ATPase activity in a concentration (1 nM-10 microM)-dependent manner in WKY rats while it failed to inhibit the enzyme activity in SHR. Dopamine (10 microM)-induced inhibition of Na+,K(+)-ATPase activity in WKY rats was significantly blocked by mepacrine (10 microM), a PLA2 inhibitor, suggesting the involvement of PLA2 in dopamine-mediated inhibition of Na+,K(+)-ATPase. Arachidonic acid (a product released by PLA2 action) inhibited Na+,K(+)-ATPase in a concentration-dependent (1-100 microM) manner in WKY rats while the inhibition in SHR was significantly attenuated (IC50: 7.5 and 80 microM in WKY rats and SHR, respectively). Furthermore, lower concentrations of arachidonic acid stimulated (30% at 1 microM) Na+,K(+)-ATPase activity in SHR. This suggests a defect in the metabolism of arachidonic acid in SHR. Proadifen (10 microM), an inhibitor of cytochrome P-450 monoxygenase (an arachidonic acid metabolizing enzyme) significantly blocked the inhibition produced by arachidonic acid in WKY rats and abolished the difference in arachidonic acid inhibition of Na+,K(+)-ATPase between WKY rats and SHR. These data suggest that PLA2 is involved in dopamine-induced inhibition of Na+,K(+)-ATPase and altered arachidonic acid metabolism may contribute to reduced dopaminergic inhibition of Na+,K(+)-ATPase activity in spontaneously hypertensive rats.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1064-1963
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
18
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
963-74
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8886479-Animals,
pubmed-meshheading:8886479-Arachidonic Acid,
pubmed-meshheading:8886479-Dopamine,
pubmed-meshheading:8886479-Dose-Response Relationship, Drug,
pubmed-meshheading:8886479-Kidney,
pubmed-meshheading:8886479-Male,
pubmed-meshheading:8886479-Phospholipases A,
pubmed-meshheading:8886479-Phospholipases A2,
pubmed-meshheading:8886479-Rats,
pubmed-meshheading:8886479-Rats, Inbred SHR,
pubmed-meshheading:8886479-Rats, Inbred WKY,
pubmed-meshheading:8886479-Sodium-Potassium-Exchanging ATPase
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Altered arachidonic acid metabolism contributes to the failure of dopamine to inhibit Na+,K(+)-ATPase in kidney of spontaneously hypertensive rats.
|
| pubmed:affiliation |
Institute for Cardiovascular Studies, College of Pharmacy, University of Houston, TX 77204-5511, USA.
|
| pubmed:publicationType |
Journal Article
|