Distinct functions of the two isoforms of dopamine D2 receptors

Alessandro Usiello, Ja-Hyun Baik, Françoise Rougé-Pont, Roberto Picetti, Andrée Dierich, Marianne LeMeur, Pier Vincenzo Piazza, Emiliana Borrelli

Research output: Contribution to journalArticle

480 Citations (Scopus)

Abstract

Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse1-7. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia8. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms9, D2S and D2L, previously thought to have the same function. Here we show that these receptors have distinct functions in vivo; D2L acts mainly at postsynaptic sites and D2S serves presynaptic autoreceptor functions. The cataleptic effects of the widely used antipsychotic haloperidol1 are absent in D2L-deficient mice. This suggests that D2L is targeted by haloperidol, with implications for treatment of neuropsychiatric disorders. The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors.

Original languageEnglish
Pages (from-to)199-203
Number of pages5
JournalNature
Volume408
Issue number6809
DOIs
Publication statusPublished - 2000 Nov 9
Externally publishedYes

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Dopamine D2 Receptors
Antipsychotic Agents
Protein Isoforms
Autoreceptors
Dopamine Receptors
Alternative Splicing
Haloperidol
Locomotion
Hormones
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • General

Cite this

Usiello, A., Baik, J-H., Rougé-Pont, F., Picetti, R., Dierich, A., LeMeur, M., ... Borrelli, E. (2000). Distinct functions of the two isoforms of dopamine D2 receptors. Nature, 408(6809), 199-203. https://doi.org/10.1038/35041572

Distinct functions of the two isoforms of dopamine D2 receptors. / Usiello, Alessandro; Baik, Ja-Hyun; Rougé-Pont, Françoise; Picetti, Roberto; Dierich, Andrée; LeMeur, Marianne; Piazza, Pier Vincenzo; Borrelli, Emiliana.

In: Nature, Vol. 408, No. 6809, 09.11.2000, p. 199-203.

Research output: Contribution to journalArticle

Usiello, A, Baik, J-H, Rougé-Pont, F, Picetti, R, Dierich, A, LeMeur, M, Piazza, PV & Borrelli, E 2000, 'Distinct functions of the two isoforms of dopamine D2 receptors', Nature, vol. 408, no. 6809, pp. 199-203. https://doi.org/10.1038/35041572
Usiello A, Baik J-H, Rougé-Pont F, Picetti R, Dierich A, LeMeur M et al. Distinct functions of the two isoforms of dopamine D2 receptors. Nature. 2000 Nov 9;408(6809):199-203. https://doi.org/10.1038/35041572
Usiello, Alessandro ; Baik, Ja-Hyun ; Rougé-Pont, Françoise ; Picetti, Roberto ; Dierich, Andrée ; LeMeur, Marianne ; Piazza, Pier Vincenzo ; Borrelli, Emiliana. / Distinct functions of the two isoforms of dopamine D2 receptors. In: Nature. 2000 ; Vol. 408, No. 6809. pp. 199-203.
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