Desensitization of the nicotinic acetylcholine receptor by diisopropylfluorophosphate

✍ Scribed by Eldefrawi, Mohyee E. ;Schweizer, Gordon ;Bakry, Nabil M. ;Valdes, James J.

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 615 KB
• Volume: 3
• Category: Article
• ISSN: 0887-2082
• DOI: 10.1002/jbt.2570030104

✦ Synopsis

The interaction of diisopropylfluorophosphate (DFP) with the nicotinic acetylcholine (ACh) receptor of Torpedo electric organ was studied, using [3H]-phencyclidine ([3H]-PCP) as a reporter probe. Phencyclidine binds with different kinetics to resting, activated, and desensitized receptor conformations. Although DFP did not inhibit binding of [3H]-ACh or 125I-alpha-bungarotoxin (BGT) to the receptor recognition sites and potentiated in a time-dependent manner [3H]-PCP binding to the receptor's high-affinity allosteric site, it inhibited the ACh- or carbamylcholine-stimulated [3H]-PCP binding. This suggested that DFP bound to a third kind of site on the receptor and affected receptor conformation. Preincubation of the membranes with DFP increased the receptor's affinity for carbamylcholine by eightfold and raised the pseudo-first-order rate of [3H]-PCP binding to that of an agonist-desensitized receptor. Accordingly, it is suggested that DFP induces receptor desensitization by binding to a site that is distinct from the recognition or high-affinity noncompetitive sites.