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Dopamine-mediated inhibition of renal Na,K-ATPase is reduced by insulin.

Authors: Banday, AA  Asghar, M  Hussain, T  Lokhandwala, MF 
Citation: Banday AA, etal., Hypertension. 2003 Jun;41(6):1353-8. Epub 2003 Apr 21.
Pubmed: (View Article at PubMed) PMID:12707290
DOI: Full-text: DOI:10.1161/01.HYP.0000069260.11830.CD

Recently we have reported that rosiglitazone treatment of obese Zucker rats reduced plasma insulin and restored the ability of dopamine to inhibit Na,K-ATPase (NKA) in renal proximal tubules. The present study was performed to test the hypothesis that a chronic increase in levels of insulin causes a decrease in expression of the D1 receptor and its uncoupling from G proteins, which may account for the diminished inhibitory effect of dopamine on NKA in obese Zucker rats. We conducted experiments in primary proximal tubule epithelial cells obtained from Sprague-Dawley rat kidneys. These cells at 80% to 90% confluence were pretreated with insulin (100 nmol/L for 24 hours) in growth factor-/serum-free medium. SKF-38393, a D1 receptor agonist, inhibited NKA activity in untreated cells, but the agonist failed to inhibit enzyme activity in insulin-pretreated cells. Basal NKA activity was similar in untreated and insulin-pretreated cells. Measurement of D1 receptors in the plasma membranes revealed that [3H]SCH-23390 binding, a D1 receptor ligand, as well as D1 receptor protein abundance, was significantly reduced in insulin-pretreated cells compared with untreated cells. SKF-38393 (10 micromol/L) elicited significant stimulation of [35S]GTPgammaS binding in the membranes from control cells, suggesting that the D1 receptor-G protein coupling was intact. However, the stimulatory effect of SKF-38393 was absent in membranes from insulin-pretreated cells. We suggest that chronic exposure of cells to insulin causes both the reduction in D1 receptor abundance and its uncoupling from G proteins. These phenomena might account for the diminished inhibitory effect of dopamine on NKA activity in hyperinsulinemic rats.

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CRRD Object Information
CRRD ID: 2302121
Created: 2008-11-19
Species: All species
Last Modified: 2008-11-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.