Antagonist binding characteristics of the Ser311-->Cys variant of human dopamine D2 receptor in vivo and in vitro.
We report in vivo and in vitro antagonist binding characteristics of the naturally occurring Ser311-->Cys variant of the human D2 dopamine receptor. Striatal receptor binding characteristics in vivo were measured with positron emission tomography and the D2 antagonist [11C]raclopride. The in vitro affinity of raclopride for the Ser311-->Cys variant and the wild type receptor was studied in membrane binding assays from stably transfected cell lines. One healthy male carrying the heterozygous Ser311-->Cys (TCC-->TGC) substitution was identified with denaturing gradient gel electrophoresis and DNA sequencing. The striatal D2 receptor binding characteristics in vivo in this subject were normal. This was supported by the in vitro data as the Ki values of raclopride for the Ser311-->Cys variant and the wild type receptor were identical. Our data suggest that the Ser311-->Cys variant of the human D2 receptor does not influence antagonist-receptor recognition in vivo or in vitro.
Pohjalainen
T
T
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Cravchik
A
A
Gejman
P V
PV
Rinne
J
J
Någren
K
K
Syvälahti
E
E
Hietala
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003545:Cysteine / Q000235:genetics*; D018492:Dopamine Antagonists / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D020891:Raclopride; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism; D012694:Serine / Q000235:genetics*; D013134:Spiperone / Q000031:analogs & derivatives / Q000378:metabolism
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D012694:Serine; D013134:Spiperone; C039167:3-N-methylspiperone; D003545:Cysteine