Demonstration of a distinct class of high-affinity binding sites for [3H]norharman [( 3H]beta-carboline) in the rat brain.
Specific binding sites were demonstrated for some beta-carbolines in the rat brain with [3H]norharman as a ligand. The ligand displayed a high affinity for synaptosomal membranes which had been fractionated by a sucrose gradient. The calculated apparent KD value was 1.55 nmol/l and the maximum number of binding sites 148 fmol/mg protein. Displacement studies showed an exclusive specificity for a small group of beta-carbolines but not for the previously described inverse agonists at the benzodiazepine receptor nor for tryptamine and other indoles, as well as pargyline, a monoamine oxidase inhibitor. Further analysis revealed other binding sites for [3H]norharman, with an apparent KD value of 36 nmol/l that are presumably located on mitochondrial membranes. Binding to these sites was also not displaced by pargyline. Pargyline displaced [3H]norharman from a third population of binding sites on mitochondrial membranes with the apparent KD value of 46 nmol/l. These findings could explain the pharmacological effects of norharman and other beta-carbolines in vivo.
Pawlik
M
M
Department of Neuropsychopharmacology, Free University, Berlin, F.R.G.
Rommelspacher
H
H
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D002243:Carbolines; D005260:Female; D005374:Filtration; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism*; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism
D000470:Alkaloids; D002243:Carbolines; D008996:Monoamine Oxidase Inhibitors; D006247:Harmine; C010262:norharman; D010293:Pargyline