Ultraviolet irradiation selectively disrupts the gamma-aminobutyric acid/benzodiazepine receptor-linked chloride ionophore

Journal Article · Mon May 01 04:00:00 EDT 1989 · Molecular Pharmacology; (USA)

OSTI ID:5641405

Evoniuk, G; Moody, E J; Skolnick, P ^[1]

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1. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (USA)

The ability of UV light to affect radioligand binding and 36Cl-uptake at the gamma-aminobutyric acidA (GABAA) receptor-chloride channel complex was examined. Exposure to 302 nm UV light produced a rapid (t1/2 = 4 min) reduction in (35S)t-butylbicyclo-phosphorothionate binding (assayed in the presence of 200 mM chloride) to sites associated with the GABAA receptor-coupled chloride ionophore. Saturation analysis revealed that this effect could be attributed entirely to a decrease in the maximum number of binding sites. Exposure to UV irradiation at lower (254 nm) and higher (366 nm) wavelengths also inhibited (35S)t-butylbicy-clophosphorothionate binding, but the respective rates of inactivation were 8- and 27-fold slower, compared with 302 nm. Other anion-dependent interactions at the GABAA receptor complex were disrupted in a similar manner. In the absence of permeant anion, (3H)flunitrazepam binding to benzodiazepine receptors was unaffected by 302 nm UV irradiation, whereas chloride-enhanced (3H)flunitrazepam binding was inhibited markedly. In the presence of 250-500 mM chloride, (3H)methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate binding to benzodiazepine receptors was also inhibited after UV exposure. Basal 36Cl- uptake into synaptoneurosomes was nearly doubled after 15 min of exposure to 302 nm light, whereas pentobarbital- and muscimol-stimulated 36Cl- uptake were reduced significantly. UV irradiation at 302 nm appears to disrupt selectively the anion-dependent functional interactions at the GABAA receptor complex. The apparent wavelength specificity suggests that the gating structure (channel) may contain tryptophan and/or tyrosine residues vital to the regulation of anion movement through the ionophore portion of this supramolecular receptor-ion channel complex.

• OSTI ID: 5641405
• Journal Information: Molecular Pharmacology; (USA), Journal Name: Molecular Pharmacology; (USA) Vol. 35:5; ISSN 0026-895X; ISSN MOPMA
• Country of Publication: United States
• Language: English

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560120 -- Radiation Effects on Biochemicals
Cells
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMAL CELLS
ANIMALS
ANIONS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CARBOXYLIC ACIDS
CHARGED PARTICLES
CHLORIDES
CHLORINE 36
CHLORINE COMPOUNDS
CHLORINE ISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
HALIDES
HALOGEN COMPOUNDS
HYDROGEN COMPOUNDS
IN VITRO
INHIBITION
IONS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
NERVE CELLS
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PROTEINS
RADIATION EFFECTS
RADIATIONS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SOMATIC CELLS
SULFUR 35
SULFUR ISOTOPES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ULTRAVIOLET RADIATION
UPTAKE
VERTEBRATES
YEARS LIVING RADIOISOTOPES