文摘
伪7尾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 伪7 and heteromeric 伪7尾2 nicotinic acetylcholine receptors in order to reveal the pharmacological consequences of 尾2 subunit incorporation into the pentamer. The non-selective agonist epibatidine did not distinguish 伪7尾2 from 伪7 nicotinic acetylcholine receptors, but three other non-selective agonists (nicotine, cytisine and varenicline) were less efficacious on 伪7尾2 than on 伪7. A more dramatic change in efficacy was seen with eight different selective 伪7 agonists. Because of their very low intrinsic efficacy, some compounds became very efficacious functional antagonists at 伪7尾2 receptors. Three 伪4尾2 nicotinic receptor selective agonists that were not active on 伪7, were also inactive on 伪7尾2, and dihydro-尾-erythroidine, an 伪4尾2 receptor-preferring antagonist, inhibited 伪7 and 伪7尾2 in a similar manner. These results reveal significant effects of 尾2 incorporation in determining the relative efficacy of several non-selective and 伪7 selective agonists, and also show that incorporation of 尾2 subunits does not cause a shift to a more 鈥溛?-like鈥?pharmacology of 伪7 nicotinic acetylcholine receptors.
