Article date: 1989/5/1
PubMed ID: 2542759
Journal name: Molecular pharmacology (ISSN: 0026-895X)
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.
Author List: Evoniuk G, Moody E J, Skolnick P
Publication Types: Journal Article
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Carbolines; Chloride Channels; Chlorides; Membrane Proteins; Receptors, GABA-A; methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; gamma-Aminobutyric Acid; Flunitrazepam; tert-butylbicyclophosphorothionate;
Mesh terms: Animals; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Carbolines/metabolism; Chloride Channels; Chlorides/metabolism; Flunitrazepam/metabolism; In Vitro Techniques; Male; Membrane Proteins; Rats; Rats, Inbred Strains; Receptors, GABA-A/metabolism; Ultraviolet Rays; gamma-Aminobutyric Acid/pharmacology;