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Striatal dopamine denervation decreases the GDP binding affinity in rat striatal membranes

A Terasmaa1, B Andbjer, K Fuxe

  • 1Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Neuroreport
|September 8, 2000
PubMed

Insights

G-protein changes in the brain

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Dopamine (DA) signaling is crucial for motor control.
  • D2 receptor supersensitivity can occur after dopamine system damage.
  • G-proteins mediate signal transduction from G protein-coupled receptors like D2.

Purpose of the Study:

  • To investigate the role of G-proteins in D2 receptor supersensitivity.
  • To understand molecular mechanisms underlying receptor changes in denervated striatum.

Main Methods:

  • Unilateral 6-hydroxydopamine (6-OHDA) induced lesions in rat nigral dopamine system.
  • Analysis of striatal membranes for [3H]raclopride binding sites and affinities.
  • Assessment of [35S]GTPgammaS and GDP binding affinities to G proteins.

Main Results:

  • Increased [3H]raclopride binding sites in denervated striatum 13 months post-lesion.
  • No significant changes in D2 receptor ligand binding affinities or high-affinity agonist sites.
  • Unaltered [35S]GTPgammaS binding affinity.
  • Decreased GDP binding affinity in DA-denervated striatum compared to intact striatum.

Conclusions:

  • Reduced GDP binding affinity to D2 receptor-coupled G proteins is implicated in D2 receptor supersensitivity.
  • This molecular alteration may contribute to functional changes after dopamine terminal degeneration.

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