What question did this study set out to answer?

To identify the signaling mechanisms by which alpha-1 adrenergic receptor stimulation activates the NHE1 and NHE3 exchanger isoforms in renal proximal tubule epithelial cells.

March 1, 2001AJP Renal Physiology

α 1 -Adrenergic receptors activate NHE1 and NHE3 through distinct signaling pathways in epithelial cells

Q: What is the clinical evidence from this study?

Intervention: alpha(1)-Adrenergic receptor stimulation vs. Unstimulated cells. Primary outcome: Na uptake.

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Key result

alpha(1)-Adrenergic receptor stimulation increased Na uptake from 8.5 to 13.8 nmol/min/mg protein, activating NHE1 via PKC and NHE3 via MAPK in renal proximal tubule cells.

Population

Epithelial cells of the renal proximal tubule (PT cells)

Comparison

alpha-Adrenergic receptor stimulation, with or… vs Sense-ODN-treated cells or untreated cells

Design

Preclinical

Authors

FLFengming LiuShandong University FGF. A. GesekDartmouth College

Discussion

Member takes

Implication

Hypothesis-generating for adrenergic control of proximal Na reabsorption; does not support clinical translation or practice changes.

Key Points

To identify the signaling mechanisms by which alpha-1 adrenergic receptor stimulation activates the NHE1 and NHE3 exchanger isoforms in renal proximal tubule epithelial cells.
Determined NHE1 and NHE3 transcript and protein expression and membrane localization in renal proximal tubule cells via Northern blotting, Western blotting, and immunolabeling.
Knocked down NHE1 and NHE3 protein expression by ~85% using streptolysin O-permeabilized delivery of isoform-specific antisense oligodeoxynucleotides.
Assessed sodium uptake and intracellular pH responses following alpha-1 adrenergic stimulation in the presence of protein kinase C inhibitor calphostin C, MAPK inhibitor PD-98059, or transfection with constitutively active MEKK1.
NHE1 localized predominantly to basolateral membranes, whereas NHE3 was expressed exclusively on the apical membrane of polarized proximal tubule cells.
Alpha-1 adrenergic receptor stimulation increased sodium uptake from 8.5 to 13.8 nmol·min⁻¹·mg protein⁻¹, a response significantly attenuated by antisense knockdown of NHE3 but unaffected by sense oligodeoxynucleotides.
Alpha-1 adrenergic activation of NHE1 was abolished by the protein kinase C inhibitor calphostin C, whereas NHE3 activation was suppressed by the MAPK inhibitor PD-98059 and selectively stimulated by truncated MEKK1.

Structured PICO

Population

Epithelial cells of the renal proximal tubule (PT cells)

Intervention

alpha(1)-Adrenergic receptor stimulation, with or without antisense oligodeoxynucleotides (AS-ODNs) for NHE1/NHE3, PKC inhibitor calphostin C, or MAPK inhibitor PD-98059

Comparator

Sense-ODN-treated cells or untreated cells

Outcome

NHE activity (measured by Na uptake and changes in intracellular pH)surrogate

Main Result

Absolute Event Rate: 13.8% vs 8.5%

In renal proximal tubule cells, alpha(1)-adrenergic receptors activate NHE1 via PKC and NHE3 via MAPK to separately regulate intracellular pH, Na absorption, and proton excretion.

Cite This Study

Liu et al. (2001) studied this question. alpha(1)-Adrenergic receptor stimulation vs. Unstimulated cells was evaluated on Na uptake. alpha(1)-Adrenergic receptor stimulation increased Na uptake from 8.5 to 13.8 nmol/min/mg protein, activating NHE1 via PKC and NHE3 via MAPK in renal proximal tubule cells.

synapsesocial.com/papers/6a8dd38dd881876296cf9501 https://doi.org/10.1152/ajprenal.2001.280.3.f415

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α 1 -Adrenergic receptors activate NHE1 and NHE3 through distinct signaling pathways in epithelial cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

α 1 -Adrenergic receptors activate NHE1 and NHE3 through distinct signaling pathways in epithelial cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

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