Modulation of brain opioid receptors by zinc and histidine

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1988

OSTI ID:7164555

Hanissian, S H

The effect of zinc and several trace elements was studied on the binding of the opioid receptor antagonist ({sup 3}H)-naloxone and the agonists ({sup 3}H)-DAGO, ({sup 3}H)-DSTLE, and ({sup 3}H)-EKC, specific for the mu, delta and kappa receptors, respectively, in several areas of the rat brain. Physiological concentrations of zinc were inhibitory to the binding of naloxone, DAGO, and EKC, whereas delta receptors were insensitive to this inhibition. Copper, cadmium, and mercury also inhibited the binding of all the ligands studied to their receptors. Histidine was most effective in preventing the inhibitory effects of zinc and copper, whereas it was less effective on cadmium, and without any effect on the inhibit was less effective on cadmium, and without any effect on the inhibition caused by mercury. Its metabolites histamine and imidazoleacetic acid, and also citrate were ineffective. Magnesium and manganese were stimulatory to opioid receptor binding, whereas cobalt and nickel had dual effects. Concentrations of zinc less that its IC{sub 50} totally prevented the stimulatory effects of magnesium and manganese on the mu and delta receptors on which zinc alone had no effects. The reducing reagents dithiothreitol and B-mercaptoethanol partially protected against zinc inhibition, and the oxidizing reagent dithiobisnitrobenzoic acid even potentiated the inhibitory effects of zinc on DSTLE and DAGO binding, although to different extents.

• Research Organization: Ohio State Univ., Columbus, OH (USA)
• OSTI ID: 7164555
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METALS
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRAIN
CADMIUM
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
COBALT
COPPER
DRUGS
ELEMENTS
ENDORPHINS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HISTIDINE
HYDROGEN COMPOUNDS
IMIDAZOLES
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
MAGNESIUM
MAMMALS
MANGANESE
MEMBRANE PROTEINS
MERCURY
METALS
NERVOUS SYSTEM
NEUROREGULATORS
NICKEL
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
REAGENTS
RECEPTORS
RODENTS
TOXICITY
TRACER TECHNIQUES
TRANSITION ELEMENTS
TRITIUM COMPOUNDS
VERTEBRATES
ZINC