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• W2074773535 abstract "Dopamine promotes sodium excretion, in part, via activation of D1 receptors in renal proximal tubules (PT) and subsequent inhibition of Na, K-ATPase. Recently, we have reported that oxidative stress causes D1 receptor–G-protein uncoupling via mechanisms involving protein kinase C (PKC) and G-protein-coupled receptor kinase 2 (GRK 2) in the primary cultures of renal PT of Sprague-Dawley (SD) rats. There are reports suggesting that redox-sensitive nuclear transcription factor, NF-κB, is activated in conditions associated with oxidative stress. This study was designed to identify the role of NF-κB in oxidative stress-induced defective renal D1 receptor–G-protein coupling and function. Treatment of the PT with hydrogen peroxide (H2O2, 50 μM/20 min) induced the nuclear translocation of NF-κB, increased PKC activity, and triggered the translocation of GRK 2 to the proximal tubular membranes. This was accompanied by hyperphosphorylation of D1 receptors and defective D1 receptor–G-protein coupling. The functional consequence of these changes was decreased D1 receptor activation-mediated inhibition of Na, K-ATPase activity. Interestingly, pretreatment with pyrrolidine dithiocarbamate (PDTC, 25 μM/10 min), an NF-κB inhibitor, blocked the H2O2-induced nuclear translocation of NF-κB, increase in PKC activity, and GRK 2 translocation and hyperphosphorylation of D1 receptors in the proximal tubular membranes. Furthermore, PDTC restored D1 receptor G-protein coupling and D1 receptor agonist-mediated inhibition of the Na, K-ATPase activity. Therefore, we suggest that oxidative stress causes nuclear translocation of NF-κB in the renal proximal tubules, which contributes to defective D1 receptor–G-protein coupling and function via mechanisms involving PKC, membranous translocation of GRK 2, and subsequent phosphorylation of dopamine D1 receptors." @default.
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• W2074773535 date "2007-03-01" @default.
• W2074773535 modified "2023-10-17" @default.
• W2074773535 title "Role of nuclear factor kappa B (NF-κB) in oxidative stress-induced defective dopamine D1 receptor signaling in the renal proximal tubules of Sprague-Dawley rats" @default.
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• W2074773535 doi "https://doi.org/10.1016/j.freeradbiomed.2006.11.033" @default.
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