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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/F1170    most recent 00119.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Izumi, Y. Articles by Tomita, K. Search for Related Content PubMed PubMed Citation Articles by Izumi, Y. Articles by Tomita, K.

Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction

Department of Nephrology, Kumamoto University, Graduate School of Medical Sciences. Kumamoto, Japan

Submitted 7 March 2008 ; accepted in final form 11 August 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 (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.

collecting ducts; transcription regulation; cell signaling