Structure and f unction of dopamine receptors

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2003 November 19 (6) Chin J Neurosci 405 ( 510280) [ ] Tourette [ ] ; ; Structure and f unction of dopamine receptors L I Fan SHU Si2yun BAO Xin2min ( I nstit ute f or Neu roscience of Fi rst M

1 2003 November 19 (6) Chin J Neurosci 405 ( ) [ ] Tourette [ ] ; ; Structure and f unction of dopamine receptors L I Fan SHU Si2yun BAO Xin2min ( I nstit ute f or Neu roscience of Fi rst M ilitary Medical U niversity Zhujiang Hospital Guangz hou China ) [ Abstract] Dopamine (DA) is the most abundant catecholaminergic neurotransmitter in the brain. The involvement and importance of DA as a neurotransmitter in the regulation of different physiological functions in the central nervous sys2 tem ( CNS) are well know. Deregulation of the dopaminergic system has been linked with Parkinson disease Tourette syndrome schizophrenia attention deficit hyperactive disorder(adhd) and generation of pituitary tumours. This review focuses on the pharmacological and biochemical features shared by the dopamine receptors. The distribution of the differ2 ent dopamine receptors in the CNS and their function especially associated with learning and memory are emphasized. [ Key words] dopamine ; dopamine receptor ; learning and memory Ξ ( ) 30 : Tourette ( l2dopa) 80 % : (1) ; (2) ; (3) ; (4) 1 ( TH) 3 42 DOPA (SNC) ( ) Ξ [ ] (2003) [ ] R981 ; R338 [ ] A [ ] [ ] [ ] [ E2mail] com [ ] (19712).

2 D2 D1 ( D1 (V TA ) D5) DA2R TATA CAAT V TA ( ) (OT) D22R ( RARE) D1 D2 4 2 mrnas (72GM) G D1 D2 [1 ] (DA2R) D12R ( CPu) ( Acb) D1 D1 D5 ( D 1A Calleja D 1B ) D2 D2 D3 D4 D1 mrna C :D12R [2 ] D52R D12R D1 D2 D22R mrna CPu OT Acb : D1 SCH (V TA) SKF D1 D5 D22R D1 [5 ] D2 mrna D2L D22R mrna D32R 3 DA2Rs D22R cdna cdna 1245 D42R mrna 415 [3 ] D2S(D2 short) D2 ( D1 D5 ) ( ) [6 \ D2L (D2 long) D2 D1 D :D1 D5 D2L D2S [3 ] D2 D1 D5 [6 ] D1 D3 446 D1 D5 GABA cdna D3 D5 [3 ] Chi n J Neurosci November (6) [4 ] [3 D1 D2 (OT) (Cx) ] D1 mrna Callija D32R [7 ; ] : D1 D D1 D5 D1 D5 [6 7 D42R 48 7 ] D1

3 407 D5 D22R Ca 2 + D22R : D1 D5 Ca 2 + D1 D1 D5 TH Ca 2 + / ( CaM CaM ) CaM Ca :D2 D1 D1 AMP2 D1 D2 [7 ] D2 ( D2 N G ) D22R D2L D2S G D4 GABA 5. 3 D22R D4 GABA (AA) Ca 2 + D4 D22R CHO AA D12R [8 GABA ] AA PTX D22R D1 D22R 5 [3 AA D12R ] 6 : D22R 6. 1 GTP2 G2 D2L G i22 : D2S 5. 1 D1 (camp) A( PKA) PKA D1 D2 D1 D2 G (D124) D2 D12 (AC) D2 R camp D22R AC ( PTX) D32R [9 ] D22R camp D22R [10 ] D32R D42R camp 5. 2 D32R D42R GH4CI D12R PKA L2 Ca 2 + N2 P2 Ca D12R T2 Ca 2 + D12R camp D2 G i/ 0 (DAT) D2L D2S G 0 Ca 2 + D22R G i N2 Ca 2 + [11 ]

4 D1 D22R D12R NMDA2R D2 quinpirole ( bromocriptine) Wilkerson [21 ] D22R D12R D22R Umegaki [22 ] D22R 14 T ( ) D22R D32R D42R D22R Greba [23 ] D22R 6. 3 Smith [24 ] D22R A10 D2L 2/ 2 [12 ] Watanabe [13 ] D2L2R Da Cunha [14 ] D2 D32R MPTP METH (metaphetamine) D22R D12R Phillips [15 ] D22R ; D22R 6. 4 Rosenkranz [16 ] PET Chi n J Neurosci November (6) Wi D1 D2 D12R De keyser J [25 ] (PFC) Sawaguchi D12R [17 ] DA sulpirde SCH23390 Hemby PFC DA SE [26 ] RNA cdna PFC Kozlov [18 ] CA1 D12D5 D12R mrna El2Ghundi 6. 5 ( LTP) [19 ] D12R Mana2 Y D1 han2vaughan [27 ] D1 D2 Baldwin remoxipride L TP ( < 4 h) D2 [20 ] D12 L TP R NMDA2R

5 409 D1/ D5 L TP 7 D1 5 G (2) : ; [ ] [ 1 ] Gingrich JA Caron M G. Rcecnt advances in the molecular biolo2 gy of dopamine receptor [ J ]. Annu Rev Neurosci : [ 2 ] Ng GY Moillac B George SR et al. Desensitization phosphory2 lation and palmitoylation of the human dopamine D1 receptor [J ]. Eur J Pharmacol (1) : [ 3 ] Jackson DM Westlind2Danielsson A. Dopamine receptors : molecular biology biochemistry and behavioural aspects [ J ]. Pharmacol Ther (2) : [4 ] Valdenaire O Vernier P Maus M et al. Transcription of the rat dopamine2d22receptor gene from two promoters [ J ]. Biochem (2) : Eur J [5 ] Civelli O Bunzow J R Grandy D K et al. Molecular biology of the dopamine receptors [J ]. Eur J Pharmacol ( 4) : [ 6 ] Smiley J F AI Levey BJ Ciliax et al. D 1 dopamine receptor im2 munoreactivity in human and monkey cerebral cortex : predomi2 nant and extrasynaptic localization in dendritic spines [ J ]. Natl Acad Sci USA (12) : Proc [7 ] Levey AI Hersch SM Rye DB et al. Localization of D 1 and spiperone and in GH 3 cells that express a D 2 2like receptor with an unusual low affinity for haloperidol in response to N GF. D 2 dopamine receptors in brain with subtype2specific antibodies [J ]. Proc Natl Acad Sci USA (19) : [8 ] Mrzlak L Bergson C Pappy M et al. Localization of dopamine D 4 receptors in GABAergic neurons of the primate brain [J ]. Na2 ture (6579) : [ 9 ] Xu M Mratalla R Gold L H et al. Dopamine D1 receptor mu2 tant mice are deficient in striatal expression of dynorphin and in dopamine2mediated behavioral responses [J ]. Cell (4) : [ 10 ] Baik J H Picetti R Saiardi A et al. Parkinsonian2like locomotor impairment in mice lacking dopamine D2 receptors [J ]. Nature (6548) : [11 ] Wise RA. Neurobiology of addiction [J ]. Curr Opin Neurobiol [12 ] Schultz W Apicella P Ljungberg T. Responses of monkey dopamine neurons to reward and conditioned stimuli during succes2 sive steps of learning a delayed response task [ J ]. J Neurosci (3) : [13 ] Watanabe M Kodama T Hikosaka K. Increase of extracellular dopamine in primate prefrontal cortex during a working memory task[j ]. J Neurophysiol (5) : [ 14 ] Da Cunha C Wietzikoski S Wietzikoski EC et al. Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system [J ]. Neurobiol Learn Mem (3) : [ 15 ] Phillips GD Setzu E Vugler A et al. Immunohistochemical as2 sessment of mesotelencephalic dopamine activity during the acqui2 sition and expression of Pavlovian versus instrumental behaviours [J ]. Neuroscience (3) : [16 ] Rosenkranz JA Grace AA. Dopamine2mediated modulation of odour2evoked amygdala potentials during Pavlovian conditioning [J ]. Nature (6886) : [ 17 ] Sawaguchi T. The effects of dopamine and its antagonists on direc2 tional delay2period activity of prefrontal neurons in monkeys dur2 ing an oculomotor delayed2response task [ J ]. Neurosci Res (2) : [ 18 ] Kozlov AP Druzin M Y Kurzina NP et al. The role of D12de2 pendent dopaminergic mechanisms of the frontal cortex in delayed responding in rats [J ]. Neurosci Behav Physiol (4) : [ 19 ] El2Ghundi M Fletcher PJ Drago J. Spatial learning deficit in dopamine D( 1) receptor knockout mice [J ]. Eur J Pharmacol (2) : [20 ] Baldwin AE Sadeghian K Kelley AE. Appetitive instrumental learning requires coincident of NMDA and dopamine D1 receptors within the medial prefrontal cortex [J ]. J Neurosci (3) : [ 21 ] Wilkerson A Levin ED. Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in rats [ J ]. science (3) : Neuro2 [ 22 ] Umegaki H Munoz J Meyer RC et al. Involvement of dopamine D ( 2) receptors in complex maze learning and acetyl2 choline release in ventral hippocampus of rats[j ]. Neuroscience (1) : [ 23 ] Greba Q Gifkins A Kokkinidis L. Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear2potentiated startle [ J ]. Brain Res ( 122 ) : 2182

6 Chi n J Neurosci November (6) 226. [24 ] Smith J W Fetsko LA Xu R et al. Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning [ J ]. Neuro2 science (4) : [ 25 ] de Keyser J De Backer J P Vauquelin G et al. The effect of ag2 ing on the D1 dopamine receptors in human frontal cortex [ J ]. Brain Res (2) : [ 26 ] Hemby SE Trojanowski J Q Ginsberg SD. Neuron2specific age2 related decreases in dopamine receptor subtype mrnas [ J ]. J Comp Neurol (2) : [27 ] Manahan2Vaughan D Alexander K. Regulation of depotentiation and long2term potentiation in the dentate gyrus of freely moving rats by dopamine D22like receptors[j ]. Cerebral Cortex (2) :

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