title: Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction.
abstract: 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 (LLC-PK1/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 NaCl- or mannitol-induced 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 Ca2+ 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-Ca2+ pathway is enhanced by hypertonicity, and 3) hypertonicity enhances the V1aR-Ca2+ pathway. The counteractivity of V2R and V1aR could be required to maintain minimum urine volume in the dehydrated state.
authors.affiliation: Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan. 053r5110@med.stud.kumamoto-u.ac.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yushi
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Hasiyet
authors.initials: H
authors.lastname: Memetimin
authors.forename: Takeaki
authors.initials: T
authors.lastname: Inoue
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Kohda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006982:Hypertonic Solutions / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D018374:LLC-PK1 Cells; D008156:Luciferases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000378:metabolism*; D013552:Swine; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D014882:Water-Electrolyte Balance / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006982:Hypertonic Solutions; D047428:Protein Kinase Inhibitors; D017483:Receptors, Vasopressin; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium