Determination of ligand binding conformations at α1-adrenergic receptor subtypes based on NMR and MD studies

Abstract

Adrenergic receptor (AR) subtypes (α1A, α1B, α1D, α2A, α2B, α2C, β1, β2, β3) are G-protein coupled receptors (GPCRs) activated by the same endogenous catecholamines, adrenaline and nor-adrenaline. The two subtypes α1A- and α1B-AR maintain a complex balance in modulating the functions of the sympathetic and central nervous systems, whereby chronic activity can be either detrimental or protective for both heart and brain function. Regulation is believed to be mediated through the distinct activation of individual α1-AR subtypes and thus, subtype selective activation or blocking may have major clinical implications. Despite having tremendous clinical importance, there are no approved α1A- or α..