17 beta-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1

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Abstract

Hofmeister MV, Damkier HH, Christensen BM, Olde B, Leeb-Lundberg LM, Fenton RA, Praetorius HA, Praetorius J. 17 beta-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1. Am J Physiol Renal Physiol 302: F358-F368, 2012. First published October 12, 2011; doi: 10.1152/ajprenal.00343.2011.-Steroid hormones such as 17 beta-estradiol (E2) are known to modulate ion transporter expression in the kidney through classic intracellular receptors. Steroid hormones are also known to cause rapid nongenomic responses in a variety of nonrenal tissues. However, little is known about renal short-term effects of steroid hormones. Here, we studied the acute actions of E2 on intracellular Ca2+ signaling in isolated distal convoluted tubules (DCT2), connecting tubules (CNT), and initial cortical collecting ducts (iCCD) by fluo 4 fluorometry. Physiological concentrations of E2 induced transient increases in intracellular Ca2+ concentration ([Ca2+](i)) in a subpopulation of cells. The [Ca2+](i) increases required extracellular Ca2+ and were inhibited by Gd3+. Strikingly, the classic E2 receptor antagonist ICI 182,780 also increased [Ca2+](i), which is inconsistent with the activation of classic E2 receptors. G proteincoupled estrogen receptor 1 (G.PER1 or GPR30) was detected in microdissected DCT2/CNT/iCCD by RT-PCR. Stimulation with the specific GPER1 agonist G-1 induced similar [Ca2+](i) increases as E2, and in tubules from GPER1 knockout mice, E2, G-1, and ICI 182,780 failed to induce [Ca2+](i) elevations. The intercalated cells showed both E2-induced concanamycin-sensitive H+-ATPase activity by BCECF fluorometry and the E2-mediated [Ca2+](i) increment. We propose that E2 via GPER1 evokes [Ca2+](i) transients and increases H+-ATPase activity in intercalated cells in mouse DCT2/CNT/iCCD.

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Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • distal renal tubules, intracellular calcium signaling, GPER1
Original languageEnglish
Pages (from-to)F358-F368
JournalAmerican Journal of Physiology-Renal Physiology
Volume302
Issue number3
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes