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 and Emiliana Borrelli ()
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Alessandro Usiello: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP
Ja-Hyun Baik: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP
Françoise Rougé-Pont: INSERM U259, Université V. Segalen Bordeaux 2
Roberto Picetti: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP
Andrée Dierich: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP
Marianne LeMeur: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP
Pier Vincenzo Piazza: INSERM U259, Université V. Segalen Bordeaux 2
Emiliana Borrelli: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP

Nature, 2000, vol. 408, issue 6809, 199-203

Abstract: Abstract Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse1,2,3,4,5,6,7. 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.

Date: 2000
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DOI: 10.1038/35041572

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