Coordinate control of prostaglandin E2 synthesis and uptake by hyperosmolarity in renal medullary interstitial cells

Michael L. Pucci, Shinichi Endo, Teruhisa Nomura, Run Lu, Cho Khine, Brenda S. Chan, Yi Bao, Victor L. Schuster

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

During water deprivation, prostaglandin E2 (PGE2), formed by renal medullary interstitial cells (RMICs), feedback inhibits the actions of antidiuretic hormone. Interstitial PGE2 concentrations represent the net of both PGE2 synthesis by cyclooxygenase (COX) and PGE2 uptake by carriers such as PGT. We used cultured RMICs to examine the effects of hyperosmolarity on both PG synthesis and PG uptake in the same RMIC. RMICs expressed endogenous PGT as assessed by mRNA and immunoblotting. RMICs rapidly took up [3H]PGE2 to a level 5- to 10-fold above background and with a characteristic time-dependent "overshoot." Inhibitory constants (Ki) for various PGs and PGT inhibitors were similar between RMICs and the cloned rat PGT. Increasing extracellular hyperosmolarity to the range of 335-485 mosM increased the net release of PGE2 by RMICs, an effect that was concentration dependent, maximal by 24 h, reversible, and associated with increased expression of COX-2. Over the same time period, there was decreased cell-surface activity of PGT due to internalization of the transporter. With continued exposure to hyperosmolarity over 7-10 days, PGE2 release remained elevated, COX-2 returned to baseline, and PGT-mediated uptake became markedly reduced. Our findings suggest that hyperosmolarity induces coordinated changes in COX-2-mediated PGE2 synthesis and PGT-mediated PGE2 uptake in RMICs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number3
DOIs
StatePublished - Mar 2006

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Dinoprostone
Kidney
Cyclooxygenase 2
Water Deprivation
Prostaglandin-Endoperoxide Synthases
Vasopressins
Immunoblotting
Messenger RNA

Keywords

  • Cyclooxygenase-2
  • Hypertonicity
  • Prostaglandin transporter

ASJC Scopus subject areas

  • Physiology

Cite this

Coordinate control of prostaglandin E2 synthesis and uptake by hyperosmolarity in renal medullary interstitial cells. / Pucci, Michael L.; Endo, Shinichi; Nomura, Teruhisa; Lu, Run; Khine, Cho; Chan, Brenda S.; Bao, Yi; Schuster, Victor L.

In: American Journal of Physiology - Renal Physiology, Vol. 290, No. 3, 03.2006.

Research output: Contribution to journalArticle

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AU - Chan, Brenda S.

AU - Bao, Yi

AU - Schuster, Victor L.

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AB - During water deprivation, prostaglandin E2 (PGE2), formed by renal medullary interstitial cells (RMICs), feedback inhibits the actions of antidiuretic hormone. Interstitial PGE2 concentrations represent the net of both PGE2 synthesis by cyclooxygenase (COX) and PGE2 uptake by carriers such as PGT. We used cultured RMICs to examine the effects of hyperosmolarity on both PG synthesis and PG uptake in the same RMIC. RMICs expressed endogenous PGT as assessed by mRNA and immunoblotting. RMICs rapidly took up [3H]PGE2 to a level 5- to 10-fold above background and with a characteristic time-dependent "overshoot." Inhibitory constants (Ki) for various PGs and PGT inhibitors were similar between RMICs and the cloned rat PGT. Increasing extracellular hyperosmolarity to the range of 335-485 mosM increased the net release of PGE2 by RMICs, an effect that was concentration dependent, maximal by 24 h, reversible, and associated with increased expression of COX-2. Over the same time period, there was decreased cell-surface activity of PGT due to internalization of the transporter. With continued exposure to hyperosmolarity over 7-10 days, PGE2 release remained elevated, COX-2 returned to baseline, and PGT-mediated uptake became markedly reduced. Our findings suggest that hyperosmolarity induces coordinated changes in COX-2-mediated PGE2 synthesis and PGT-mediated PGE2 uptake in RMICs.

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