Interaction of narcotic antagonist naltrexone with nicotinic acetylcholine receptor. 1987

L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.

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.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D011950 Receptors, Cholinergic Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D002038 Bungarotoxins Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms. alpha-Bungarotoxin,beta-Bungarotoxin,kappa-Bungarotoxin,alpha Bungarotoxin,beta Bungarotoxin,kappa Bungarotoxin
D004557 Electric Organ In about 250 species of electric fishes, modified muscle fibers forming disklike multinucleate plates arranged in stacks like batteries in series and embedded in a gelatinous matrix. A large torpedo ray may have half a million plates. Muscles in different parts of the body may be modified, i.e., the trunk and tail in the electric eel, the hyobranchial apparatus in the electric ray, and extrinsic eye muscles in the stargazers. Powerful electric organs emit pulses in brief bursts several times a second. They serve to stun prey and ward off predators. A large torpedo ray can produce of shock of more than 200 volts, capable of stunning a human. (Storer et al., General Zoology, 6th ed, p672) Electric Organs,Organ, Electric,Organs, Electric
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D000664 Amphibian Venoms Venoms produced by frogs, toads, salamanders, etc. The venom glands are usually on the skin of the back and contain cardiotoxic glycosides, cholinolytics, and a number of other bioactive materials, many of which have been characterized. The venoms have been used as arrow poisons and include bufogenin, bufotoxin, bufagin, bufotalin, histrionicotoxins, and pumiliotoxin. Frog Venoms,Toad Venoms,Amphibian Venom,Frog Venom,Toad Venom,Venom, Amphibian,Venom, Frog,Venom, Toad,Venoms, Amphibian,Venoms, Frog,Venoms, Toad
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001001 Anura An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae. Bombina,Frogs and Toads,Salientia,Toad, Fire-Bellied,Toads and Frogs,Anuras,Fire-Bellied Toad,Fire-Bellied Toads,Salientias,Toad, Fire Bellied,Toads, Fire-Bellied
D014101 Torpedo A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays. Electric Rays,Torpedinidae,Rays, Electric

Related Publications

L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
March 1985, FEBS letters,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
August 1991, The Journal of pharmacology and experimental therapeutics,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
August 1978, The International journal of the addictions,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
February 2000, European journal of pharmacology,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
February 2006, The Journal of pharmacology and experimental therapeutics,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
January 2003, Journal of proteome research,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
October 1998, The Journal of pharmacology and experimental therapeutics,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
October 1983, Brain research,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
March 1990, Biochemical and biophysical research communications,
L Oliveira, and B W Madsen, and N Kapai, and S M Sherby, and K L Swanson, and M E Eldefrawi, and E X Albuquerque
June 1974, The American journal of psychiatry,
Copied contents to your clipboard!