What question did this study set out to answer?

To determine whether ambient osmolarity modulates endothelin responsiveness and receptor signaling pathways in renal medullary interstitial cells.

July 1, 1995Journal of Clinical InvestigationOpen Access

Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.

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Population

Cultured rat renal medullary interstitial cells and glomerular mesangial cells

Comparison

Hyperosmolar culture medium achieved by addition… vs Isosmolar culture medium (300 mOsm/kg H2O)

Design

Preclinical

Follow-up

3 to 24 hours

Authors

MVMelchiore A. VernaceNewYork–Presbyterian Hospital PMP. F. MentoPfizer (United States)MMMasashi MaitaTokyo University of Marine Science and Technology

Discussion

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Implication

Does not inform clinical practice; leaves open in vivo relevance of hyperosmolar ETA regulation in renal medulla.

Key Points

To determine whether ambient osmolarity modulates endothelin responsiveness and receptor signaling pathways in renal medullary interstitial cells.
Cultured rat renal medullary interstitial cells were exposed for 3 to 24 hours to isosmolar (300 mOsm/kg H2O) or urea-induced hyperosmolar (600 mOsm/kg H2O) media.
Assayed endothelin-evoked intracellular calcium transients, prostaglandin E2 synthesis, endothelin-A receptor density via binding kinetics, and mRNA expression via Northern blot analysis.
In hyperosmolar medium, peak endothelin-evoked calcium transients were blunted by 45% to 58% (P < 0.02) and prostaglandin E2 accumulation dropped from 16-fold to 2-fold above basal levels (P < 0.001).
Endothelin-A receptor density decreased by 84% under hyperosmolar conditions (238 ± 12 vs. 1450 ± 184 fmol/mg, P < 0.01), despite a 58% increase in endothelin-A receptor mRNA levels (P < 0.05).

Structured PICO

Population

Cultured rat renal medullary interstitial cells (RMICs) (passages 18-74) and glomerular mesangial cells (passages 11-18)

Intervention

Hyperosmolar culture medium (600 mOsm/kg H2O) achieved by addition of urea, sodium chloride plus urea, or mannitol for 3 to 24 hours

Comparator

Isosmolar culture medium (300 mOsm/kg H2O)

Outcome

Endothelin-evoked intracellular Ca2+ transient, PGE2 accumulation, and ETA receptor density and mRNA expressionsurrogate

Hyperosmolarity blunts endothelin signaling in renal medullary interstitial cells via receptor downregulation, despite an increase in receptor mRNA.

Cite This Study

Vernace et al. (1995) studied this question.

synapsesocial.com/papers/6a953ba1d33c5efb307cfbc4 https://doi.org/10.1172/jci118019

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Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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