Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic
The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxyl (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.
- Research Organization:
- California Univ., Santa Cruz, CA (USA)
- OSTI ID:
- 5642526
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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ACETYLCHOLINE
RECEPTORS
ANESTHETICS
BIOCHEMICAL REACTION KINETICS
PIPERIDINES
CELL MEMBRANES
ELECTRON SPIN RESONANCE
FISHES
INHIBITION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AQUATIC ORGANISMS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAGNETIC RESONANCE
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
PYRIDINES
QUATERNARY COMPOUNDS
REACTION KINETICS
RESONANCE
VERTEBRATES
550201* - Biochemistry- Tracer Techniques