Abstract
Here, we investigated the binding characteristics of [ 3 H ] N-(2,5-dimethoxybenzyl)- N-(5-fluoro-2-phenoxyphenyl)acetamide ([ 3 H ]DAA1106), a potent and selective ligand for peripheral benzodiazepine receptors, in mitochondrial fractions of the rat brain. [ 3 H ]DAA1106 bound to the mitochondrial fraction of the rat brain in a saturable manner. The dissociation constant ( K d) and maximal number of binding sites ( B max) obtained from Scatchard plot analysis of the saturation curve of [ 3 H ]DAA1106 binding were 0.12±0.03 nM and 161.03±5.80 fmol/mg protein, respectively. [ 3 H ]DAA1106 binding to mitochondrial preparations of the rat cerebral cortex was inhibited by several peripheral benzodiapine receptor ligands, and DAA1106 was the most potent inhibitor in inhibiting [ 3 H ]DAA1106 binding among the peripheral benzodiazepine receptor ligands we tested. The binding of [ 3 H ]DAA1106 was not affected by several neurotransmitter-related compounds, including adrenoceptor, γ-aminobutyric acid (GABA), dopamine, 5-hydroxytryptamine (5-HT), acetylcholine, histamine, glutamate and central benzodiazepine receptor ligands even at a concentration of 10 μM. In the cerebral cortex of rhesus monkeys, DAA1106 and 1-(2-chlorophenyl)- N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) potently inhibited [ 3 H ]DAA1106 binding, while 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydrobenzo[ e][1,4]diazepin-2-one (Ro5-4864) did not. The highest [ 3 H ]DAA1106 binding was observed in the olfactory bulb, followed by the cerebellum. In autoradiographic studies, practically the same results were obtained, in that the highest binding of [ 3 H ]DAA1106 was in the olfactory bulb. Potent labeling was also noted in ventricular structures such as the choroid plexus. Thus, [ 3 H ]DAA1106 is a potent and selective ligand for peripheral benzodiazepine receptors and should prove useful for elucidating the physiological relevance of events mediated through peripheral benzodiazepine receptors.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.