Unique pharmacology of heteromeric α7β2 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.
α7β2 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 α7 and heteromeric α7β2 nicotinic acetylcholine receptors in order to reveal the pharmacological consequences of β2 subunit incorporation into the pentamer. The non-selective agonist epibatidine did not distinguish α7β2 from α7 nicotinic acetylcholine receptors, but three other non-selective agonists (nicotine, cytisine and varenicline) were less efficacious on α7β2 than on α7. A more dramatic change in efficacy was seen with eight different selective α7 agonists. Because of their very low intrinsic efficacy, some compounds became very efficacious functional antagonists at α7β2 receptors. Three α4β2 nicotinic receptor selective agonists that were not active on α7, were also inactive on α7β2, and dihydro-β-erythroidine, an α4β2 receptor-preferring antagonist, inhibited α7 and α7β2 in a similar manner. These results reveal significant effects of β2 incorporation in determining the relative efficacy of several non-selective and α7 selective agonists, and also show that incorporation of β2 subunits does not cause a shift to a more “β2-like” pharmacology of α7 nicotinic acetylcholine receptors.
Ruud
R
Zwart
Merrick
M
Strotton
Jennifer
J
Ching
Peter C
PC
Astles
Emanuele
E
Sher
D000818:Animals; D015870:Gene Expression; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2