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Related Experiment Videos

Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype.

E Fedele1, G Fontana, C Munari

  • 1Departimento de Medicina Sperimentale, Sezione de Farmacologia e Tossicologie, Viale Cembrano 4, 16148 Genova, Italy.

The European Journal of Neuroscience
|June 26, 1999
PubMed
Summary

Human brain dopamine (DA) autoreceptors regulating DA release are confirmed to be of the D2 subtype. This research clarifies the specific receptor type involved in controlling dopamine release in the human brain.

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Area of Science:

  • Neuropharmacology
  • Neuroscience
  • Dopamine Receptor Research

Background:

  • Dopamine (DA) autoreceptors on nerve terminals modulate DA release.
  • Rodent studies suggest these autoreceptors are primarily of the D2 type.
  • The DA receptor family includes D2, D3, and D4 subtypes.

Purpose of the Study:

  • To investigate and classify native human dopamine autoreceptors for the first time.
  • To determine the specific subtype of dopamine autoreceptors regulating dopamine release in the human neocortex.
  • To compare findings in human brain tissue with established rodent models.

Main Methods:

  • Studied the release of [3H]DA evoked by electrical stimulation in fresh human neocortical slices.
  • Utilized D2/D3 receptor agonist quinpirole and antagonists (-)-sulpiride, S 14297 (D3-selective), and L-745,870 (D4-selective).

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  • Compared results with rat neocortical and striatal slices, and rat mesencephalic neuronal cultures.

    • Main Results:

    • In human neocortical slices, quinpirole inhibited [3H]DA release with an EC50 of 17 nM, indicating D2/D3 receptor involvement.
    • The D2/D3 antagonist (-)-sulpiride shifted quinpirole's concentration-response curve, with an apparent pA2 of 8.5.
    • D3-selective (S 14297) and D4-selective (L-745,870) antagonists did not affect quinpirole's inhibitory effects, confirming D2 subtype specificity.

    Conclusions:

    • Human brain dopamine autoreceptors regulating DA release in the terminal region are of the D2 subtype.
    • Findings align with those in rat striatal slices and neuronal cultures, but differ from rat cortical slices.
    • This study definitively classifies native human dopamine autoreceptors as D2 subtype.