ANTAGONIST BINDING CHARACTERISTICS OF THE SER(311)-]CYS VARIANT OF HUMAN DOPAMINE D-2 RECEPTOR IN-VIVO AND IN-VITRO

We report in vivo and in vitro antagonist binding characteristics of t he naturally occurring Ser(311)-->Cys variant of the human D-2 dopamin e receptor. Striatal receptor binding characteristics in vivo were mea sured with positron emission tomography and the D-2 antagonist [C-11]r aclopride. The in vitro affinity of raclopride for the Ser(311)-->Cys variant and the wild type receptor was studied in membrane binding ass ays from stably transfected cell lines. One healthy male carrying the heterozygous Ser(311)-->Cys (TCC->TGC) substitution was identified wit h denaturing gradient gel electrophoresis and DNA sequencing. The stri atal D-2 receptor binding characteristics in vivo in this subject were normal. This was supported by the in vitro data as the Ki values of r aclopride for the Ser(311)-->Cys variant and the wild type receptor we re identical. Our data suggest that the Ser(311)-->Cys variant of the human D-2 receptor does not influence antagonist-receptor recognition in vivo or in vitro. (C) 1997 Academic Press.