Unique pharmacology of heteromeric α7β2 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes

alpha 7 beta 2 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 alpha 7 and heteromeric alpha 7 beta 2 nicotinic acetylcholine receptors in order to reveal the pharmacological consequences of beta 2 subunit incorporation into the pentamer, The non-selective agonist epibatidine did not distinguish alpha 7 beta 2 from alpha 7 nicotinic acetylcholine receptors, but three other non-selective agonists (nicotine, cytisine and varenicline) were less efficacious on alpha 7 beta 2 than on alpha 7.A more dramatic change in efficacy was seen with eight different selective alpha 7 agonists. Because of their very low intrinsic efficacy, some compounds became very efficacious functional antagonists at alpha 7 beta 2 receptors. Three alpha 7 beta 2 nicotinic receptor selective agonists that were not active on alpha 7, were also inactive on alpha 7 beta 2, and dihydro-beta-erythroidine, an alpha 7 beta 2 receptor-preferring antagonist, inhibited alpha 7 and alpha 7 beta 2 in a similar manner. These results reveal significant effects of beta 2 incorporation in determining the relative efficacy of several non-selective and alpha 7 selective agonists, and also show that incorporation of beta 2 subunits does not cause a shift to a more "beta 2-like" pharmacology of alpha 7 nicotinic acetylcholine receptors. (C) 2014 Elsevier B.V. All rights reserved.