PT  - JOURNAL ARTICLE
AU  - R Link
AU  - D Daunt
AU  - G Barsh
AU  - A Chruscinski
AU  - B Kobilka
TI  - Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes and identification of a single amino acid in the mouse alpha 2-C10 homolog responsible for an interspecies variation in antagonist binding.
DP  - 1992 Jul 01
TA  - Molecular Pharmacology
PG  - 16--27
VI  - 42
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/42/1/16.short
4100  - http://molpharm.aspetjournals.org/content/42/1/16.full
SO  - Mol Pharmacol1992 Jul 01; 42
AB  - Molecular cloning and ligand binding studies have shown the alpha 2 class of adrenergic receptor (alpha 2-AR) to be a family of at least three related subtypes in humans. These studies have not, however, identified distinct subtype-specific functions for these receptors in vivo. It should be possible to extend the analysis of alpha 2-AR subtype function to the animal level through the use of experimental mammalian embryology in mice. To begin this process, we have isolated two mouse genomic clones encoding alpha 2-AR subtypes and expressed these genes in COS-7 cells for binding studies. Sequence homology and ligand binding data allow the assignment of one clone (M alpha 2-4H) as the mouse homolog of the human alpha 2-C4 subtype. The other clone (M alpha 2-10H) closely resembles the human alpha 2-C10 subtype in sequence but binds with significantly lower affinity to yohimbine and rauwolscine, members of a distinct class of bulky alpha 2-selective antagonists commonly used to evaluate alpha 2-AR function in vivo. To define the domain(s) responsible for this unusual binding property, we constructed a series of M alpha 2-10H/human alpha 2-C10 chimeric receptors. Analysis of these receptors identified a conservative Cys201 to Ser201 change in the fifth transmembrane domain of M alpha 2-10H as being responsible for the low affinity of the mouse receptor for yohimbine.