title: Stereochemical requirements of alpha 2-adrenergic receptors for alpha-methyl substituted phenethylamines.
abstract: The alpha 1- and alpha 2-adrenergic effects of the stereoisomers of alpha-methyldopamine were evaluated in guinea pig aorta and field-stimulated guinea pig ileum, respectively, in order to establish the stereochemical requirements of these receptors for alpha-methyl substituted phenethylamines. The alpha 1-adrenergic receptor did not distinguish between the stereoisomers of alpha-methyldopamine which is in marked contrast to the alpha 2-adrenergic receptor where a dramatic stereochemical preference for the 2S(+)-isomer was observed. In addition, 2R(-)-alpha-methyldopamine displayed no alpha-receptor subtype specificity whereas 2S(+)-alpha-methyldopamine was highly selective (23 fold) for the alpha 2-adrenergic receptor. These results indicate that the alpha 2-adrenergic receptor can recognize and accept methyl substituents at the alpha-carbon atom of phenethylamines when correctly oriented, while the alpha 1-adrenergic receptor cannot. Thus, the alpha-carbon atom is a major determinant of the alpha 2-adrenergic effects of phenethylamines, and plays an important role in determining alpha-receptor subtype specificity. It is hypothesized that the alpha 2-adrenergic receptor (but not alpha 1) has an additional recognition site which will accommodate alpha-substituted phenethylamines.
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D003846:Deoxyepinephrine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D008771:Nordefrin / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D010627:Phenethylamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003846:Deoxyepinephrine; D008771:Nordefrin; D004298:Dopamine; D009638:Norepinephrine