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• W4236074177 abstract "Dopamine receptor type 1 (D 1 R) and angiotensin receptor type 2 (AT 2 R) uncoupling from their intracellular second messengers are implicated in both salt sensitivity of blood pressure (SS) and hypertension. Angiotensin III (Ang III) and dopamine (DA) work cooperatively through binding to the interdependent D 1 R and AT 2 R to regulate renal sodium balance through autocrine signaling pathways. Aminopeptidase N (APN) is a renin-angiotensin system (RAS) enzyme localized in RPTC responsible for converting the natriuretic peptide AngIII into the anti-natriuretic agonist angiotensin IV (AngIV). The expression of APN (measured by a fluorescently labelled CD13 antibody) was investigated after increasing intracellular salt concentration with both the ionophore monensin (100 μM, 1hr.) and NaCl buffer solution (50 mmol/L, 1 hr.) in known G protein coupled (i22) and G protein uncoupled (i19) RPTC. Increasing intracellular sodium resulted in a more dramatic decrease in overall APN expression in uncoupled cells (i19 vehicle (VEH) 1.00 ± 0.03, Mon 0.87 ± 0.01 fold, n=3, p<0.05) compared to a slight decrease in coupled cells (i22 VEH 1.00 ± 0.01, NaCl 0.96 ± 0.01 fold, n=6, p<0.05). Two unknown coupling urine cell lines (RMC031-202 and RMC031-6) were evaluated alongside these known cells in an attempt to classify each as coupled or uncoupled. RMC031-202 replicated i22 (coupled) trends while RMC031-6 closely replicated i19 (uncoupled) data. Moreover, baseline APN expression comparison (normalized to i22) between the cell lines reveled a significantly elevated baseline for known and suspected uncoupled cells (i19 1.69 ± 0.047, RMC031-6 2.01 ± 0.004 fold over i22, n=3, p<0.05). Known (i22) and suspected (RMC031-202) normally coupled cells had equivalent baselines (p>0.05). An uncoupling defect may result in decreased APN regulation in RPTC causing higher baseline levels of APN expression. These increased levels of APN, in turn, lead not only to amplified production of the anti-natriuretic agonist AngIV but also reduced potential for cooperative natriuretic AngIII/DA autocrine signaling thus disrupting the dopaminergic system’s ability to suppress RAS and maintain proper sodium balance." @default.
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• W4236074177 date "2017-09-01" @default.
• W4236074177 modified "2023-09-27" @default.
• W4236074177 title "Abstract P326: Effects of D 1 R/AT 2 R Coupling on Aminopeptidase N (APN) in Human Renal Proximal Tubule Cells (RPTC)" @default.
• W4236074177 doi "https://doi.org/10.1161/hyp.70.suppl_1.p326" @default.
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