Zwart_2014_Eur.J.Pharmacol_726C_77

alpha7beta2 is a novel type of nicotinic acetylcholine receptor shown to be uniquely expressed in cholinergic neurons of the basal forebrain and in hippocampal interneurons. We have compared the pharmacological properties of recombinant homomeric alpha7 and heteromeric alpha7beta2 nicotinic acetylcholine receptors in order to reveal the pharmacological consequences of beta2 subunit incorporation into the pentamer. The non-selective agonist epibatidine did not distinguish alpha7beta2 from alpha7 nicotinic acetylcholine receptors, but three other non-selective agonists (nicotine, cytisine and varenicline) were less efficacious on alpha7beta2 than on alpha7. A more dramatic change in efficacy was seen with eight different selective alpha7 agonists. Because of their very low intrinsic efficacy, some compounds became very efficacious functional antagonists at alpha7beta2 receptors. Three alpha4beta2 nicotinic receptor selective agonists that were not active on alpha7, were also inactive on alpha7beta2, and dihydro-beta-erythroidine, an alpha4beta2 receptor-preferring antagonist, inhibited alpha7 and alpha7beta2 in a similar manner. These results reveal significant effects of beta2 incorporation in determining the relative efficacy of several non-selective and alpha7 selective agonists, and also show that incorporation of beta2 subunits does not cause a shift to a more "beta2-like" pharmacology of alpha7 nicotinic acetylcholine receptors.