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Interaction of narcotic antagonist naltrexone with nicotinic acetylcholine receptor
- Source :
- European journal of pharmacology. 140(3)
- Publication Year :
- 1987
-
Abstract
- The interactions of naltrexone with the nicotinic acetylcholine receptor were studied electrophysiologically using the frog sciatic nerve-sartorius muscle and biochemically using membranes from the electric organ of Torpedo ocellata. At nanomolar concentrations naltrexone increased the peak amplitude of endplate currents with little change in the decay time constant. At micromolar concentrations there was a concentration-dependent depression of endplate current and miniature endplate current amplitudes and decay time constants. Decay time constant depression was enhanced with hyperpolarization. Only marginal curvature was induced in peak endplate current amplitude versus membrane voltage plots by naltrexone. Naltrexone had no effect on single channel conductance but decreased open channel lifetime, according to fluctuation analysis. Naltrexone alone (less than or equal to 3 microM) did not impair binding of [125I]alpha-bungarotoxin to the receptor in a fast pre-equilibration assay, but increased the ability of acetylcholine to displace [125I]alpha-bungarotoxin. The drug displaced the agonist-stimulated binding of [3H]perhydrohistrionicotoxin to the channel site. Biphasic functional changes in neuromuscular transmission can be attributed to an allosteric mechanism with increased agonist binding to the nicotinic receptor at nanomolar concentrations and caused a non-competitive blockade of the ionic channel at micromolar concentrations.
- Subjects :
- Agonist
medicine.medical_specialty
medicine.drug_class
Neuromuscular transmission
In Vitro Techniques
Torpedo
Naltrexone
Iodine Radioisotopes
Internal medicine
medicine
Animals
Receptors, Cholinergic
Pharmacology
Electric Organ
Narcotic antagonist
Chemistry
Hyperpolarization (biology)
Bungarotoxins
Electrophysiology
Nicotinic acetylcholine receptor
Endocrinology
Nicotinic agonist
Amphibian Venoms
Anura
Acetylcholine
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 140
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....33cd9a656c78179f334a64338b654ce0