cAMP-dependent protein kinase A mediation of vasopressin gene expression in the hypothalamus of the osmotically challenged rat

Mol Cell Neurosci. 2003 Sep;24(1):82-90. doi: 10.1016/s1044-7431(03)00123-4.

Abstract

We have tested the hypothesis that 3', 5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is involved in the regulation of the vasopressin (VP) gene in the magnocellular neurons of the paraventricular nucleus (PVN) of the osmotically challenged rat. An adenoviral vector expressing a potent peptide inhibitor of PKA, Ad.CMV.PKIalpha, was demonstrated to be highly efficient in vitro. Ad.CMV.PKIalpha was then introduced into the PVN of rats bearing a VP reporter transgene (3-VCAT-3) consisting of the VP structural gene containing an epitope reporter in exon III, flanked by 3 kb of upstream and 3 kb of downstream sequence Robust transgene expression is seen in VP neurons of the PVN, and this increases following 72 h of dehydration. Ad.CMV.PKIalpha significantly blunted 3-VCAT-3 expression in the osmotically stimulated PVN. Our evidence suggests that PKA mediates changes in VP gene expression in response to dehydration through sequences contained within the 3-VCAT-3 transgene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dehydration / genetics
  • Dehydration / metabolism
  • Female
  • Gene Expression Regulation / physiology*
  • Genes, Reporter / genetics
  • Genetic Vectors / pharmacology
  • Hypothalamo-Hypophyseal System / enzymology*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Paraventricular Hypothalamic Nucleus / enzymology*
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / pharmacology
  • Transgenes / genetics
  • Vasopressins / biosynthesis
  • Vasopressins / genetics*
  • Water-Electrolyte Balance / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Pkia protein, rat
  • Recombinant Fusion Proteins
  • Vasopressins
  • Cyclic AMP-Dependent Protein Kinases