RT Journal Article
SR Electronic
T1 Four Pharmacologically Distinct Subtypes of α4β2 Nicotinic Acetylcholine Receptor Expressed in <em>Xenopus laevis</em>Oocytes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1124
OP 1131
DO 10.1124/mol.54.6.1124
VO 54
IS 6
A1 Ruud Zwart
A1 Henk P. M. Vijverberg
YR 1998
UL http://molpharm.aspetjournals.org/content/54/6/1124.abstract
AB Nicotinic receptors generally are presumed to consist of two α and three non-α subunits. We varied the relative levels of expression of the neuronal nicotinic α4 and β2 receptor subunits inXenopus laevis oocytes by nuclear injection of cDNAs coding for these subunits in α:β ratios of 9:1, 1:1, and 1:9. The sensitivities of the receptors to acetylcholine andd-tubocurarine were investigated in voltage-clamp experiments. For receptors expressed at the 9:1 and 1:1 α:β ratios, the EC50 value of acetylcholine is ∼60 μm. For the majority of the receptors expressed at the 1:9 α:β ratio, the sensitivity to acetylcholine is enhanced 30-fold. No evidence for more than one type of acetylcholine binding site in a single receptor is obtained. The sensitivity to d-tubocurarine decreases with decreasing α:β ratio. IC50 values ofd-tubocurarine are 0.2, 0.5, and 2 μm for the 9:1, 1:1, and 1:9 α:β ratios, respectively. At the 1:9 α:β ratio, additional receptors with an IC50 value of 163 μm d-tubocurarine are expressed. At least two components with distinct sensitivities tod-tubocurarine are required to account for the shift in IC50. The combined agonist and antagonist effects reveal four distinct subtypes of α4β2 nicotinic receptors. The results imply that the subunit stoichiometry of heteromeric α4β2 acetylcholine receptors is not restricted to 2α:3β.