Modulation of brain opioid receptors by zinc and histidine
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
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Multiple opioid receptor binding in dissociated intact guinea pig brain cells
Differential regulation of. mu. , delta, kappa opioid receptors by Mn/sup + +/
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CADMIUM
BIOCHEMICAL REACTION KINETICS
TOXICITY
COBALT
COPPER
ENDORPHINS
RECEPTORS
HISTIDINE
BIOLOGICAL EFFECTS
MAGNESIUM
MANGANESE
MERCURY
NICKEL
ZINC
BRAIN
INHIBITION
LIGANDS
RATS
REAGENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METALS
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DRUGS
ELEMENTS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMIDAZOLES
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
TRANSITION ELEMENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques