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Sensitivity to voltage-independent inhibition determined by pore-lining region of the acetylcholine receptor.
Francis MM
,
Choi KI
,
Horenstein BA
,
Papke RL
.
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Some noncompetitive inhibitors (e.g., ganglionic blockers) exhibit selectivity for the inhibition of neuronal nicotinic acetylcholine receptors (nAChRs). This study characterizes the mechanism of selective long-term inhibition of neuronal and muscle-neuronal chimeric nAChRs by bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate (bis-TMP-10 or BTMPS), a bifunctional form of the potent ganglionic blocker tetramethylpiperidine. Long-term inhibition of neuronal nAChRs by bis-TMP-10 has been previously demonstrated to arise, at least in part, from the binding of the bis compound to neuronal beta-subunits. In this study, long-term inhibition is demonstrated to be dependent upon the presence of sequence element(s) within the pore-lining second transmembrane domain (tm2) of neuronal beta-subunits; however, the inhibitor binding site itself does not appear to be contained within the segment of the channel pore influenced by the membrane electric field. Specifically, our results imply that bis-TMP-10 interacts with an activation-sensitive element, the availability of which may be regulated by a sequence in the tm2 domain. Furthermore, we demonstrate a compound length requirement for long-term inhibition that would be consistent with binding to multiple sites located on the extracellular portion of the receptor.
Akabas,
Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
1992,
Pubmed
,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994,
Pubmed
,
Xenbase
Anand,
Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure.
1991,
Pubmed
,
Xenbase
Ascher,
Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells.
1979,
Pubmed
Bertrand,
Activation and blocking of neuronal nicotinic acetylcholine receptor reconstituted in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Boulter,
Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family.
1987,
Pubmed
,
Xenbase
Changeux,
The functional architecture of the acetylcholine nicotinic receptor explored by affinity labelling and site-directed mutagenesis.
1992,
Pubmed
Charnet,
An open-channel blocker interacts with adjacent turns of alpha-helices in the nicotinic acetylcholine receptor.
1990,
Pubmed
Conroy,
Neurons can maintain multiple classes of nicotinic acetylcholine receptors distinguished by different subunit compositions.
1995,
Pubmed
Cooper,
Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor.
1991,
Pubmed
DiPaola,
Mapping the alpha-subunit site photolabeled by the noncompetitive inhibitor [3H]quinacrine azide in the active state of the nicotinic acetylcholine receptor.
1990,
Pubmed
Francis,
Muscle-type nicotinic acetylcholine receptor delta subunit determines sensitivity to noncompetitive inhibitors, while gamma subunit regulates divalent permeability.
1996,
Pubmed
,
Xenbase
Gerzanich,
"Orphan" alpha6 nicotinic AChR subunit can form a functional heteromeric acetylcholine receptor.
1997,
Pubmed
,
Xenbase
Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: serine-262 of the delta subunit is labeled by [3H]chlorpromazine.
1986,
Pubmed
Giraudat,
Structure of the high-affinity binding site for noncompetitive blockers of the acetylcholine receptor: [3H]chlorpromazine labels homologous residues in the beta and delta chains.
1987,
Pubmed
Glossmann,
A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker.
1993,
Pubmed
Holtzman,
Electron microscopy of complexes of isolated acetylcholine receptor, biotinyl-toxin, and avidin.
1982,
Pubmed
Horton,
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
1989,
Pubmed
Ifune,
Inward rectification of acetylcholine-elicited currents in rat phaeochromocytoma cells.
1992,
Pubmed
Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase
Karlin,
The arrangement of the subunits of the acetylcholine receptor of Torpedo californica.
1983,
Pubmed
Karlin,
Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.
1995,
Pubmed
Kearney,
Determinants of nicotinic receptor gating in natural and unnatural side chain structures at the M2 9' position.
1996,
Pubmed
,
Xenbase
LEE,
1:2:2:6:6-Pentamethylpiperidine: a new hypotensive drug.
1958,
Pubmed
Leonard,
Evidence that the M2 membrane-spanning region lines the ion channel pore of the nicotinic receptor.
1988,
Pubmed
,
Xenbase
Luetje,
Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors.
1991,
Pubmed
,
Xenbase
Machold,
The handedness of the subunit arrangement of the nicotinic acetylcholine receptor from Torpedo californica.
1995,
Pubmed
Miller,
Genetic manipulation of ion channels: a new approach to structure and mechanism.
1989,
Pubmed
Neher,
Local anaesthetics transiently block currents through single acetylcholine-receptor channels.
1978,
Pubmed
Papke,
Mechanisms of noncompetitive inhibition of acetylcholine-induced single-channel currents.
1989,
Pubmed
Papke,
The role of the beta 4-subunit in determining the kinetic properties of rat neuronal nicotinic acetylcholine alpha 3-receptors.
1991,
Pubmed
,
Xenbase
Papke,
The kinetic properties of neuronal nicotinic receptors: genetic basis of functional diversity.
1993,
Pubmed
Papke,
Inhibition of nicotinic acetylcholine receptors by bis (2,2,6,6-tetramethyl- 4-piperidinyl) sebacate (Tinuvin 770), an additive to medical plastics.
1994,
Pubmed
,
Xenbase
Pedersen,
Structure of the noncompetitive antagonist-binding site of the Torpedo nicotinic acetylcholine receptor. [3H]meproadifen mustard reacts selectively with alpha-subunit Glu-262.
1992,
Pubmed
Sands,
Neuronal nicotinic acetylcholine receptor currents in phaeochromocytoma (PC12) cells: dual mechanisms of rectification.
1992,
Pubmed
Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed
Sargent,
The diversity of neuronal nicotinic acetylcholine receptors.
1993,
Pubmed
White,
Agonist-induced changes in the structure of the acetylcholine receptor M2 regions revealed by photoincorporation of an uncharged nicotinic noncompetitive antagonist.
1992,
Pubmed
Zhorov,
Dimensions of the ion channel in neuronal nicotinic acetylcholine receptor as estimated from analysis of conformation-activity relationships of open-channel blocking drugs.
1991,
Pubmed
