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• W2071125949 abstract "The pharmacological specificity of a nicotinic acetylcholine receptor (nAChR) optical biosensor was investigated using three fluorescein isothiocyanate (FITC)-tagged neurotoxic peptides that vary in the reversibility of their receptor inhibition: α-bungarotoxin (α-BGT), α-Naja toxin (α-NT), and α-conotoxin (GI) (α-CNTX). Kinetic analysis of the time course of binding of FITC-neurotoxins to the nAChR-coated fiber gave association rate constants (k+1) of 8.4 × 106 m−1 for FITC-α-BGT, 6.0 × 106 m−1 min−1 for FITC-α-NT and 1.4 × 106 m−1 min−1 for FITC-α-CNTX. THe dissociation rate constants (k−1) for the three neurotoxins were 7.9 × 10−3 min−1, 4.8 × 10−2 min−1 and 8.0 × 10−1 min−1 for FITC-α-BGT, FITC-α-NT and FITC-α-CNTX, respectively. The equilibrium dissociation constant (Kd) values for the three toxins, calculated from these rare constants, were similar to published values obtained from tissue responses or ligand binding assays. The optical signal generated by FTC-α-NT binding to the nAChR-coated fiber was effectively quenched by agonists and antagonists of the nAChR but not by most of the tested agonists and antagonists of muscarinic cholinergic, adrenergic, glutamatergic, serotonergic, dopaminergic or GABAergic receptors. Interestingly, 5-hydroxytryptamine, haloperidol and (+)cis-misthyldioxolane gave significant inhibition of FITC-α-NT binding to the immobilized receptor. Equilibrium constants of inhibition (Ki) for d-tubocurarine (d-TC) and carbamylcholine (carb) were determined from competition studies using FITC-α-CNTX, FITC-α-NT or FITC-α-BGT as probes for receptor occupancy. When the more reversible probe FITC-α-CNTX was used, the Ki value for d-TC was an order of magnitude lower than those determined using the less reversible probes. Ki values for carb, however, were independent independent of the FITC-toxin probe used." @default.
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• W2071125949 date "1991-01-01" @default.
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• W2071125949 title "Pharmacological specificity of a nicotinic acetylcholine receptor optical sensor" @default.
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• W2071125949 doi "https://doi.org/10.1016/0956-5663(91)85048-2" @default.
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