Analysis of the conserved Asp(114) residue of the dopamine D2 receptor in schizophrenic patients.
The factors that influence response to antipsychotics treatment in chlorpromazine remain difficult to delineate but are thought to include genetic factors. Site-directed mutagenesis studies have demonstrated that substitution of the conserved residues Asp(113) to an Asn or Glu greatly reduces the binding affinity of propranolol in the beta-adrenergic receptor and the substitution of an Asp(114) has similar effects in the dopamine D2 receptor. In this study we have found the Asp(114) in the dopamine D2 receptor to be unaltered in 72 unrelated schizophrenic individuals including 12 patients classified according to their response to chlorpromazine.
Shaikh
S
S
Department of Psychological Medicine, Institute of Psychiatry, London, UK.
Hodgkinson
S
S
Pilowsky
L
L
Van Os
J
J
Vallada
H
H
Collier
D
D
Gill
M
M
D001224:Aspartic Acid / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D002746:Chlorpromazine / Q000378:metabolism / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
D017448:Receptors, Dopamine D2; D001224:Aspartic Acid; D002746:Chlorpromazine