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Phorbol ester differentially regulates oxytocin receptor binding activity in hypothalamic cultured neurons and

M T Strosser1, M E Evrard, C Breton

  • 1Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR 7519, CNRS ULP, 21 rue René Descartes, 67084, Strasbourg Cedex, France.

Peptides
|April 20, 2001
PubMed

Insights

Protein kinase C (PKC) activation has opposing effects on oxytocin receptors in hypothalamic neurons and astrocytes. However, PKC is not involved in oxytocin-induced receptor downregulation in these cells.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Oxytocin receptors mediate crucial physiological functions.
  • Understanding oxytocin receptor regulation is vital for neuroscience.
  • Protein kinase C (PKC) is implicated in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of PKC in oxytocin receptor (OTR) downregulation in cultured hypothalamic neurons and astrocytes.
  • To determine if PKC activation influences OTR binding activity.
  • To elucidate the cellular mechanisms of OTR regulation.

Main Methods:

  • Primary cultures of hypothalamic neurons and astrocytes were utilized.
  • Effects of PKC activator (phorbol-myristate-acetate, PMA) and inhibitor (bisindolylmaleimide) on OTR binding were assessed.
  • Oxytocin (OT) treatment was used to induce receptor downregulation.
  • RT-PCR, subcloning, and sequencing were performed for OTR mRNA analysis.

Main Results:

  • PKC activation by PMA increased OTR antagonist binding in neurons but decreased it in astrocytes.
  • The PKC inhibitor prevented PMA-induced changes in OTR binding.
  • OT-induced OTR downregulation was not affected by the PKC inhibitor in either cell type.
  • PMA modulated OT-induced downregulation differently in neurons and astrocytes.
  • Neuronal and astrocyte OTR mRNA sequences were identical to the rat uterine receptor.

Conclusions:

  • PKC activation exerts opposing effects on OTR binding activity in hypothalamic neurons and astrocytes.
  • PKC is not involved in the mechanism of OT-induced OTR downregulation.
  • Hypothalamic OTRs in neurons and astrocytes share sequence homology with peripheral receptors.

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