Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements

Am J Physiol. 1997 Apr;272(4 Pt 2):F443-50. doi: 10.1152/ajprenal.1997.272.4.F443.


Vasopressin plays an essential role for the regulation of water balance by activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here we present evidence that vasopressin may also act as a long-term, transcriptional regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally express V2 receptor (V2R) and which were transfected with a fragment of the human AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive element binding protein (CREB) and expression of c-Fos. Binding of these factors to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation. These results establish the role of vasopressin as a regulator of transcription and are the first example of how a message from a highly specific receptor is, via a dual effect of the cAMP signal on CREB and immediate early gene expression, transduced to the transcription of a final target protein with known biological effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins*
  • Binding Sites
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Deamino Arginine Vasopressin / pharmacology
  • Gene Expression Regulation
  • Humans
  • Ion Channels / biosynthesis
  • Ion Channels / genetics*
  • Kinetics
  • Models, Biological
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Phosphorylation
  • Promoter Regions, Genetic* / drug effects
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Receptors, Vasopressin / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism*
  • Transfection
  • Vasopressins / pharmacology*


  • AQP2 protein, human
  • Aquaporin 2
  • Aquaporin 6
  • Aquaporins
  • Cyclic AMP Response Element-Binding Protein
  • Ion Channels
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Receptors, Vasopressin
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Vasopressins
  • Phorbol 12,13-Dibutyrate
  • Cyclic AMP
  • Chloramphenicol O-Acetyltransferase
  • Adenylyl Cyclases
  • Deamino Arginine Vasopressin