Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites

Journal Article · Tue Feb 21 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00430a038· OSTI ID:5649464

Forman, S A; Miller, K W ^[1]

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1. Harvard Univ., Cambridge, MA (USA)

The relationship between the high-affinity procaine channel inhibition site and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid {sup 86}Rb{sup +} quenched-flux assays at 4 {degree}C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with {alpha}-bungarotoxin ({alpha}-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations alone, AChR undergoes one phase of inactivation in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting ACh concentrations rapid inactivation complete in 30-75 ms is followed by fast desensitization at the same k{sub d} observed without procaine. The dependence of k{sub r} on (procaine) is consistent with a bimolecular association between procaine and its AChR site. Inhibition of AChR function by mixtures of procaine plus self-inhibiting concentrations of ACh or suberyldicholine was studied by reducing the level of {alpha}-BTX block in vesicles. The data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and k{sub r}'s dependence on (ACh) in channel-activating range closely parallels that of {sup 86}Rb{sup +} flux response to ACh.

• OSTI ID: 5649464
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:4; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
ALKALI METAL ISOTOPES
AMINES
AMMONIUM COMPOUNDS
ANESTHETICS
ANTIGENS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DAYS LIVING RADIOISOTOPES
DRUGS
ESTERS
INACTIVATION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
MATERIALS
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROCAINE
PROTEINS
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RUBIDIUM 86
RUBIDIUM ISOTOPES
TOXIC MATERIALS
TOXINS
UPTAKE