Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

Article Details

Citation

Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB

Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

Nature. 1991 Apr 18;350(6319):614-9.

PubMed ID
1826762 [ View in PubMed
]
Abstract

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
D(1B) dopamine receptorP21918Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ApomorphineDopamine D1 receptorKi (nM)680N/AN/ADetails
ApomorphineDopamine D5 receptorKi (nM)363N/AN/ADetails
BromocriptineDopamine D1 receptorKi (nM)672N/AN/ADetails
BromocriptineDopamine D5 receptorKi (nM)454N/AN/ADetails
ChlorpromazineDopamine D1 receptorKi (nM)73N/AN/ADetails
ChlorpromazineDopamine D5 receptorKi (nM)133N/AN/ADetails
ClozapineDopamine D1 receptorKi (nM)141N/AN/ADetails
DopamineDopamine D1 receptorKi (nM)2340N/AN/ADetails
DopamineDopamine D5 receptorKi (nM)228N/AN/ADetails
FenoldopamDopamine D1 receptorKi (nM)28N/AN/ADetails
FenoldopamDopamine D1 receptorKi (nM)1818N/AN/ADetails
FenoldopamDopamine D5 receptorKi (nM)800N/AN/ADetails
FenoldopamDopamine D5 receptorKi (nM)15N/AN/ADetails
FlupentixolDopamine D1 receptorKi (nM)4N/AN/ADetails
FluphenazineDopamine D1 receptorKi (nM)21N/AN/ADetails
HaloperidolDopamine D1 receptorKi (nM)27N/AN/ADetails
RotigotineDopamine D1 receptorKi (nM)2172N/AN/ADetails
RotigotineDopamine D5 receptorKi (nM)986N/AN/ADetails
ThioridazineDopamine D1 receptorKi (nM)100N/AN/ADetails