Four Pharmacologically Distinct Subtypes of α4β2 Nicotinic Acetylcholine Receptor Expressed inXenopus laevisOocytes
- 1 December 1998
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET)
- Vol. 54 (6), 1124-1131
- https://doi.org/10.1124/mol.54.6.1124
Abstract
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 μmd-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.Keywords
This publication has 23 references indexed in Scilit:
- Differential co-expression of nicotinic acetylcholine receptor α4 and β2 subunit genes in various regions of rat brainNeuroReport, 1996
- Physiological Diversity of Nicotinic Acetylcholine Receptors Expressed by Vertebrate NeuronsAnnual Review of Physiology, 1995
- Nicotinic receptor: an allosteric protein specialized for intercellular communicationSeminars in Neuroscience, 1995
- Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of residues that determine curare selectivity.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptorNature, 1991
- Activation and blocking of neuronal nicotinic acetylcholine receptor reconstituted in Xenopus oocytes.Proceedings of the National Academy of Sciences of the United States of America, 1990
- Single-channel currents of rat neuronal nicotinic acetylcholine receptors expressed in xenopus oocytesNeuron, 1989
- Molecular basis of the two nonequivalent ligand binding sites of the muscle nicotinic acetylcholine receptorNeuron, 1989
- Distribution of alpha2, alpha3, alpha4, and beta2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: A hybridization histochemical study in the ratJournal of Comparative Neurology, 1989
- Properties of neuronal type acetylcholine receptors in voltage clamped mouse neuroblastoma cellsNeuroscience, 1989