title: 17β-Estradiol induces nongenomic effects in renal intercalated cells through G protein-coupled estrogen receptor 1.
abstract: Steroid hormones such as 17β-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 Ca(2+) 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 Ca(2+) concentration ([Ca(2+)](i)) in a subpopulation of cells. The [Ca(2+)](i) increases required extracellular Ca(2+) and were inhibited by Gd(3+). Strikingly, the classic E2 receptor antagonist ICI 182,780 also increased [Ca(2+)](i), which is inconsistent with the activation of classic E2 receptors. G protein-coupled estrogen receptor 1 (GPER1 or GPR30) was detected in microdissected DCT2/CNT/iCCD by RT-PCR. Stimulation with the specific GPER1 agonist G-1 induced similar [Ca(2+)](i) increases as E2, and in tubules from GPER1 knockout mice, E2, G-1, and ICI 182,780 failed to induce [Ca(2+)](i) elevations. The intercalated cells showed both E2-induced concanamycin-sensitive H(+)-ATPase activity by BCECF fluorometry and the E2-mediated [Ca(2+)](i) increment. We propose that E2 via GPER1 evokes [Ca(2+)](i) transients and increases H(+)-ATPase activity in intercalated cells in mouse DCT2/CNT/iCCD.
authors: Dept. of Biomedicine, The Water and Salt Research Center, Aarhus Univ., Aarhus C, Denmark.
authors: Marlene Vind
authors: MV
authors: Hofmeister
authors: Helle Hasager
authors: HH
authors: Damkier
authors: Birgitte Mønster
authors: BM
authors: Christensen
authors: Björn
authors: B
authors: Olde
authors: L M
authors: LM
authors: Fredrik Leeb-Lundberg
authors: Robert A
authors: RA
authors: Fenton
authors: Helle A
authors: HA
authors: Praetorius
authors: Jeppe
authors: J
authors: Praetorius
mesh_terms: D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007685:Kidney Tubules, Collecting / Q000378:metabolism* / Q000648:ultrastructure; D007686:Kidney Tubules, Distal / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000450:Aldosterone; D004958:Estradiol; D006180:Proton-Translocating ATPases; D002118:Calcium