Aarhus University Seal

Jørgen Frøkiær

Acute effects of vasopressin V2-receptor antagonist on kidney AQP2 expression and subcellular distribution

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
The acute effect of treatment with the vasopressin V2-receptor antagonist OPC-31260 (OPC) on aquaporin-2 (AQP2) distribution and expression in rat kidney was examined. Immunofluorescence and semi-quantitative immunoelectron microscopy revealed that 15 and 30 min of OPC treatment resulted in significant reduction in apical plasma membrane labeling of AQP2, with a concomitant increase in labeling of vesicles and multivesicular bodies. In parallel, OPC treatment induced a large increase in urine output [0.6 +/- 0.2 vs. 8.3 +/- 1.0 ml/h (n = 4)]. Northern blotting using a 32P-labeled AQP2 cDNA probe and a digoxigenin-labeled AQP2 RNA probe revealed a band of approximately 1.6 kb corresponding to the predicted size of AQP2 mRNA. In control experiments, thirsting increased, whereas water loading decreased AQP2 mRNA levels. Treatment of rats with OPC caused a significant reduction in AQP2 mRNA within 30 min (52 +/- 21%, n = 8, P <0.025) and 60 min (56 +/- 7%, n = 4, P <0.001) of treatment compared with intravenous saline-injected controls. Thus a very rapid reduction in AQP2 mRNA was observed in response to vasopressin-receptor antagonist treatment. The reduction in AQP2 mRNA persisted after 24 h (40 +/- 17%, n = 5, P <0.05) of OPC treatment. There was a parallel increase in diuresis and reduction in urine osmolality. In conclusion, V2-receptor blockade produced a rapid internalization of AQP2 parallel with a rapid increase in urine output. Furthermore, OPC treatment caused a rapid and significant reduction in AQP2 mRNA expression, demonstrating that for rapid regulation of AQP2 expression, modulation of AQP2 mRNA levels is regulated via vasopressin-receptor signaling pathways.
Original languageEnglish
JournalAmerican Journal of Physiology (Consolidated)
Issue2 Pt 2
Pages (from-to)F285-97
Publication statusPublished - 1998

    Research areas

  • Animals, Aquaporin 2, Aquaporin 6, Aquaporins, Benzazepines, Cell Membrane, Diuresis, Immunohistochemistry, Ion Channels, Kidney, Kidney Medulla, Kidney Tubules, Collecting, Male, Microscopy, Immunoelectron, RNA, Messenger, Rats, Rats, Wistar, Receptors, Vasopressin, Subcellular Fractions, Thirst, Transcription, Genetic

See relations at Aarhus University Citationformats

ID: 32951861