Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding.

Publisher Website
Google Scholar
Abstract
[3H]Diazepam appeared to bind specifically to a single, saturable, binding site located on rat brain membranes, with an affinity constant near 3 nM at pH 7.4. Specific binding constituted more than 90% of total binding at 0.degree. and less than 10% of total binding at 37.degree.. Arrhenius plots suggested a sharp conformational change in the diazepam receptor near 18.degree.. Mitochondrial fractions from rat kidney, liver and lung exhibited some [3H]diazepam binding that could be displaced by nonradioactive diazepam and several other benzodiazepines. Ro-4864, which is almost inactive in displacing [3H]diazepam from brain membranes, was extremely potent in displacing it from kidney mitochondria. Clonazepam, the most potent inhibitor of brain binding, was an extremely weak inhibitor of kidney binding. Diazepam binding to kidney mitochondria had an affinity constant of 40 nM, about 15 times higher than that in brain. No specific diazepam binding was detected in intestine or skeletal muscle. Specific [3H]diazepam binding to membranes appeared to be restricted to brain, where it was unevenly distributed: the density of diazepam receptors was about 5 times higher in cortex (the highest density) than in pons-medulla (lowest density). Trypsin and chymotrypsin completely abolished specific [3H]diazepam binding in brain and kidney.