PMID:11089973

Citation	Usiello, A, Baik, JH, Rougé-Pont, F, Picetti, R, Dierich, A, LeMeur, M, Piazza, PV and Borrelli, E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408:199-203
Abstract	Signalling through dopamine D2 receptors governs physiological functions related to locomotion, hormone production and drug abuse. D2 receptors are also known targets of antipsychotic drugs that are used to treat neuropsychiatric disorders such as schizophrenia. By a mechanism of alternative splicing, the D2 receptor gene encodes two molecularly distinct isoforms, 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 haloperidol 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.
Links	PubMed Online version:10.1038/35041572
Keywords	Animals; Apomorphine/pharmacology; Benzazepines/pharmacology; Catalepsy/metabolism; Chimera; Dopamine/metabolism; Dopamine Agonists/pharmacology; Dopamine Antagonists/pharmacology; Haloperidol/pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis; Protein Isoforms/chemistry; Protein Isoforms/physiology; Quinpirole/pharmacology; Receptors, Dopamine D2/chemistry; Receptors, Dopamine D2/genetics; Receptors, Dopamine D2/physiology; Signal Transduction; Spiperone/pharmacology; Synapses/physiology
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