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

  • Wong L
  • Harding T
  • Uney J
 et al. 
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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.PKIα, was demonstrated to be highly efficient in vitro. Ad.CMV.PKIα 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.PKIα 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. © 2003 Elsevier Science (USA). All rights reserved.

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Authors

  • Liang Fong Wong

  • Tom Harding

  • James Uney

  • David Murphy

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