RT Journal Article
SR Electronic
T1 Modulation by calcium of gamma-aminobutyric acid (GABA) binding to GABAA and GABAB recognition sites in rat brain. Involvement of different mechanisms.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 352
OP 359
VO 25
IS 3
A1 Majewska, M D
A1 Chuang, D M
YR 1984
UL http://molpharm.aspetjournals.org/content/25/3/352.abstract
AB Calcium modulates sodium-independent binding of gamma-aminobutyric acid (GABA) to GABAA and GABAB recognition sites located in synaptic membranes of rat brain. At 37 degrees the binding of [3H]GABA to the GABAB recognition site is dramatically stimulated by Ca2+ with an EC50 (half-saturation constant) of congruent to 10 microns, whereas the binding to the GABAA recognition site is only slightly, but significantly, potentiated by Ca2+ with an EC50 of congruent to 0.1-1.0 micron. The effect of calcium on GABAA recognition sites requires a temperature of 37 degrees and the presence of calmodulin. Only GABAA recognition sites are linked to benzodiazepine recognition sites, and the interaction between these sites is modulated by Ca2+ at physiological ion concentrations. When free Ca2+ in the assay medium is below 10 nM, only one population of low-affinity GABAA recognition sites can be measured; however, when free Ca2+ is at the micromolar level, or if diazepam is present, a high affinity-binding site appears in addition to the pre-existing low-affinity component. On the basis of affinity there is a single population of GABAB bindings sites, but the number of sites is about 90% greater at 37 degrees than at 4 degrees. This temperature-dependent increase in the number of GABAB recognition sites is calmodulin-independent, and data with leupeptin, hemin, and antipain suggest that this temperature-dependent increase in GABAB sites might involve the activity of Ca2+-dependent protease(s).