Regulation of V 2 R transcription by hypertonicity and V 1 aRV 2 R signal interaction

Izumi Y, Nakayama Y, Memetimin H, Inoue T, Kohda Y, Nonoguchi H, Tomita K. Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. Am J Physiol Renal Physiol 295: F1170–F1176, 2008. First published August 13, 2008; doi:10.1152/ajprenal.00119.2008.—Arginine vasopressin (AVP) and hypertonicity in the renal medulla play a major role in the urine concentration mechanism. Previously, we showed that rat vasopressin V2 receptor (rV2R) promoter activity was increased by vasopressin V2R stimulation and decreased by vasopressin V1a receptor (V1aR) stimulation in a LLC-PK1 cell line stably expressing rat V1aR (LLCPK1/rV1aR). In the present study, we investigated the effects of hypertonicity on the rV2R promoter activity and on the suppression of rV2R promoter activity by V1aR stimulation in LLC-PK1/rV1aR cells. rV2R promoter activity was increased in NaClor mannitolinduced hypertonicity. The hypertonicity-responsive site in the rV2R promoter region was limited to 10 bp, including the Sp1 motif. The increase of V2R promoter activity by hypertonicity was significantly inhibited by a JNK inhibitor (SP600125) and PKA inhibitor (H89). In contrast, rV2R promoter activity was remarkably suppressed by V1aR stimulation in the hypertonic condition rather than in the isotonic condition. The AVP-stimulated intracellular Ca concentration was increased in the hypertonic condition, suggesting the functional activation of V1aR by hypertonicity. In conclusion, 1) V2R promoter activity is increased by hypertonicity via the JNK and PKA pathways, 2) suppression of V2R expression by the V1aR-Ca pathway is enhanced by hypertonicity, and 3) hypertonicity enhances the V1aRCa pathway. The counteractivity of V2R and V1aR could be required to maintain minimum urine volume in the dehydrated state.

[1]  K. Tomita,et al.  Vasopressin regulates the renin-angiotensin-aldosterone system via V1a receptors in macula densa cells. , 2008, American journal of physiology. Renal physiology.

[2]  S. Nielsen,et al.  Cellular and subcellular distribution of the type-2 vasopressin receptor in the kidney. , 2007, American journal of physiology. Renal physiology.

[3]  Tomohiko Mori,et al.  Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway. , 2007, American journal of physiology. Renal physiology.

[4]  A. Tanoue,et al.  Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. , 2007, Endocrinology.

[5]  K. Tomita,et al.  Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis. , 2007, American journal of physiology. Renal physiology.

[6]  Shuyi Wang,et al.  Vasopressin promotes cardiomyocyte hypertrophy via the vasopressin V1A receptor in neonatal mice. , 2007, European journal of pharmacology.

[7]  Q. Cai,et al.  Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct. , 2007, American journal of physiology. Renal physiology.

[8]  Z. Karim,et al.  Regulation of ROMK (Kir 1.1) Channel Expression in Kidney Thick Ascending Limb by Hypertonicity: Role of TonEBP and MAPK Pathways , 2006, Nephron Physiology.

[9]  R. Schrier,et al.  cAMP regulates vasopressin-induced AQP2 expression via protein kinase A-independent pathway. , 2006, Biochimica et biophysica acta.

[10]  U. Hasler,et al.  Tonicity-responsive enhancer binding protein is an essential regulator of aquaporin-2 expression in renal collecting duct principal cells. , 2006, Journal of the American Society of Nephrology : JASN.

[11]  G. Tsujimoto,et al.  V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. R. Sheen,et al.  How tonicity regulates genes: story of TonEBP transcriptional activator , 2006, Acta physiologica.

[13]  F. Ismail-Beigi,et al.  Control of Glut1 promoter activity under basal conditions and in response to hyperosmolarity: role of Sp1. , 2006, American journal of physiology. Cell physiology.

[14]  Y. Terada,et al.  Differential Effects of Hyperosmolality on Na-K-ATPase and Vasopressin-Dependent cAMP Generation in the Medullary Thick Ascending Limb and Outer Medullary Collecting Duct , 2005, Hypertension Research.

[15]  K. Kasono,et al.  Hypertonicity regulates the aquaporin-2 promoter independently of arginine vasopressin. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[16]  A. Bellanger,et al.  Inverse PCR-mediated cloning of the promoter for the rat vasopressin V2 receptor gene , 1995, Pflügers Archiv.

[17]  Lixia Zhao,et al.  Vasopressin-Induced Cytoplasmic and Nuclear Calcium Signaling in Embryonic Cortical Astrocytes: Dynamics of Calcium and Calcium-Dependent Kinase Translocation , 2003, The Journal of Neuroscience.

[18]  R. Schrier,et al.  Hypertonicity-induced Aquaporin-1 (AQP1) Expression Is Mediated by the Activation of MAPK Pathways and Hypertonicity-responsive Element in the AQP1 Gene* , 2003, The Journal of Biological Chemistry.

[19]  W. Rosenthal,et al.  Osmolality and solute composition are strong regulators of AQP2 expression in renal principal cells. , 2003, American journal of physiology. Renal physiology.

[20]  M. Burg,et al.  cAMP-independent role of PKA in tonicity-induced transactivation of tonicity-responsive enhancer/ osmotic response element-binding protein , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Schrier,et al.  Identification and characterization of a novel hypertonicity-responsive element in the human aquaporin-1 gene. , 2002, Biochemical and biophysical research communications.

[22]  C. Smith,et al.  Structure and characterization of the mouse UT-A gene (Slc14a2). , 2002, American journal of physiology. Renal physiology.

[23]  J. Frøkiaer,et al.  Aquaporins in the kidney: from molecules to medicine. , 2002, Physiological reviews.

[24]  L. Bankir,et al.  Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects. , 2001, Cardiovascular research.

[25]  R. Star,et al.  Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats , 2001, Pflügers Archiv.

[26]  J. Shabb.  Physiological substrates of cAMP-dependent protein kinase. , 2001, Chemical reviews.

[27]  Y. Nakayama,et al.  The TonE/TonEBP Pathway Mediates Tonicity-responsive Regulation of UT-A Urea Transporter Expression* , 2000, The Journal of Biological Chemistry.

[28]  R. Nemenoff,et al.  Induction of Smooth Muscle α-Actin in Vascular Smooth Muscle Cells by Arginine Vasopressin Is Mediated by c-Jun Amino-terminal Kinases and p38 Mitogen-activated Protein Kinase* , 2000, The Journal of Biological Chemistry.

[29]  J. Sands.  Regulation of urea transporter proteins in kidney and liver. , 2000, The Mount Sinai journal of medicine, New York.

[30]  F. Park,et al.  Regional time-dependent changes in vasopressin V2 receptor expression in the rat kidney during water restriction. , 1998, American journal of physiology. Renal physiology.

[31]  D. Ausiello,et al.  Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells. , 1997, The American journal of physiology.

[32]  T. Berl,et al.  Multiple mitogen-activated protein kinases are regulated by hyperosmolality in mouse IMCD cells. , 1997, The American journal of physiology.

[33]  C. Jean,et al.  Isolation of the Mouse Aldose Reductase Promoter and Identification of a Tonicity-responsive Element* , 1997, The Journal of Biological Chemistry.

[34]  M. Knepper.  Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. , 1997, The American journal of physiology.

[35]  F. Marumo,et al.  Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts. , 1995, The Journal of clinical investigation.

[36]  M. Imai,et al.  Electrophysiological study of luminal and basolateral vasopressin in rabbit cortical collecting duct. , 1995, The American journal of physiology.

[37]  I. Teitelbaum.  Protein kinase C inhibits arginine vasopressin-stimulated cAMP accumulation via a Gi-dependent mechanism. , 1993, The American journal of physiology.

[38]  M. Breyer,et al.  cAMP-dependent protein kinase mediates hydrosmotic effect of vasopressin in collecting duct. , 1992, The American journal of physiology.

[39]  M. Brownstein,et al.  Distribution of V1a and V2 vasopressin receptor messenger ribonucleic acids in rat liver, kidney, pituitary and brain. , 1992, Endocrinology.

[40]  K. Tabei,et al.  Luminal vasopressin modulates transport in the rabbit cortical collecting duct. , 1991, The Journal of clinical investigation.

[41]  R. Anderson,et al.  Phorbol esters inhibit adenylate cyclase activity in cultured collecting tubular cells. , 1988, The American journal of physiology.

[42]  K. Skorecki,et al.  Effects of hypertonicity on cAMP production in cultured renal epithelial cells (LLC-PK1). , 1987, Mineral and electrolyte metabolism.