Involvement of the first transmembrane segment of human α(2) -adrenoceptors in the subtype-selective binding of chlorpromazine, spiperone and spiroxatrine.

ABSTRACT:

Background and purpose

Some large antagonist ligands (ARC239, chlorpromazine, prazosin, spiperone, spiroxatrine) bind to the human α(2A) -adrenoceptor with 10- to 100-fold lower affinity than to the α(2B)- and α(2C)-adrenoceptor subtypes. Previous mutagenesis studies have not explained this subtype selectivity.

Experimental approach

The possible involvement of the extracellular amino terminus and transmembrane domain 1 (TM1) in subtype selectivity was elucidated with eight chimaeric receptors: six where TM1 and the N-terminus were exchanged between the α(2)-adrenoceptor subtypes and two where only TM1 was exchanged. Receptors were expressed in CHO cells and tested for ligand binding with nine chemically diverse antagonist ligands. For purposes of interpretation, molecular mo

SUBMITTER: Laurila JM 

PROVIDER: S-EPMC3221108 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature