Effects of thio-group modification and Ca/sup 2 +/ on agonist-specific state transitions of a central nicotinic acetylcholine receptor

Journal Article · Tue May 29 04:00:00 EDT 1979 · Biochemistry; (United States)

OSTI ID:5435790

Lukas, R J; Morimoto, H; Bennett, E L

Agonist-binding affinities of central nervous system nicotinic acetylcholine receptors (nAcChR) are sensitive to the duration of exposure to agonist. These agonist-induced changes in receptor state may be mimicked by appropriate modification of receptor thio groups and/or by manipulation of solvent ionic composition. In the absence of Ca/sup 2 +/, the concentration of acetylcholine (AcCh) necessary to prevent half of specific /sup 3/H-labeled ..cap alpha..-bungarotoxin binding is 1 mM for nAcChR treated with dithiothreitol (DTT) or DTT-N-ethylmaleimide (low-affinity states) and 40 ..mu..M for nAcChR treated with DTT-5,5'-dithiobis(2-nitrobenzoic acid) or for native nAcChR pretreated with AcCh (high-affinity states). Addition of Ca/sup 2 +/ results in an increase in the effectiveness of AcCh toward blocking toxin binding. None of these treatments alters toxin or antagonist binding nor are there observed differences in Hill numbers for agonist binding. Agonists competitively inhibit toxin binding to low-affinity states, but noncompetitive inhibition is observed for binding to high-affinity states. Values of AcCh dissociation constants estimated from these data fall within the range of values determined physiologically with nAcChR from other systems. The data indicate that the redox state of brain nAcChR thio groups and Ca/sup 2 +/ may mediate physiologically important changes in the receptor state during activation and desensitization.

• Research Organization: Univ. of California, Berkeley
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 5435790
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 18:11; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
ALKALINE EARTH METAL COMPOUNDS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANIMALS
AZINES
BINDING ENERGY
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
CALCIUM COMPOUNDS
CARBOXYLIC ACIDS
CATIONS
CENTRAL NERVOUS SYSTEM
CHARGED PARTICLES
CHEMICAL BONDS
CHEMISTRY
DATA
DATA FORMS
DRUGS
ENERGY
ESTERS
EXPERIMENTAL DATA
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INFORMATION
INHIBITION
IONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATHEMATICAL MODELS
NERVE CELLS
NERVOUS SYSTEM
NICOTINIC ACID
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASYMPATHOMIMETICS
PHYSIOLOGY
PYRIDINES
QUATERNARY COMPOUNDS
RATS
REACTION KINETICS
RECEPTORS
RESPONSE MODIFYING FACTORS
RODENTS
SOMATIC CELLS
TABLES
TRITIUM COMPOUNDS
VERTEBRATES
VITAMIN B GROUP
VITAMINS