Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction
| Autor: | Hiroshi Nonoguchi, Yukimasa Kohda, Kimio Tomita, Yuichiro Izumi, Hasiyet Memetimin, Takeaki Inoue, Yushi Nakayama |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Receptors
Vasopressin Vasopressin medicine.medical_specialty Transcription Genetic Arginine MAP Kinase Signaling System Swine Physiology Hypertonic Solutions Biology Transfection p38 Mitogen-Activated Protein Kinases Arginine vasopressin receptor 2 Internal medicine medicine Transcriptional regulation Renal medulla Animals Kidney Tubules Collecting Extracellular Signal-Regulated MAP Kinases Luciferases Promoter Regions Genetic Receptor Protein Kinase Inhibitors Kidney JNK Mitogen-Activated Protein Kinases Water-Electrolyte Balance Rats medicine.anatomical_structure Endocrinology LLC-PK1 Cells Calcium Signal transduction |
| Zdroj: | American Journal of Physiology-Renal Physiology. 295:F1170-F1176 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|