Characterization of binding sites for the omega3 receptor ligands [3H]PK11195 and [3H]RO5-4864 in human brain

European Journal of Pharmacology
V L Rao, R F Butterworth

Abstract

The kinetics and pharmacology of the isoquinoline and benzodiazepine binding sites of the omega3 or peripheral-type benzodiazepine receptors were studied using the specific ligands [3H] 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin -2-one ([3H]PK11195) and [3H]1-(2-Chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarb oxamide ([3H]RO5-4864), respectively. Binding of both ligands was saturable, reversible, displayed nanomolar affinity, and best fit to a single site model. Occipital cortex and cerebellum displayed highest and lowest densities of binding sites respectively; for both ligands. Bmax values of [3H]PK11195 were several-fold higher than that of [3H]RO5-4864 in all regions studied consistent with their binding to distinct subunits of the human peripheral-type benzodiazepine receptor heteromeric complex. However, the isoquinoline and benzodiazepine ligands were found to be mutually competitive at nanomolar concentrations suggesting allosteric interactions between these two sites. Competition binding experiments showed that the binding of both ligands was displaced by diazepam with Ki values in the nM range, and by clonazepam in the microM range. The novel peripheral-type benzodiazepine rec...Continue Reading

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Citations

Oct 2, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Fabien ChauveauBertrand Tavitian
Sep 19, 2008·Journal of Neuropathology and Experimental Neurology·Sriram VennetiClayton A Wiley
Apr 29, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·David R OwenChristine A Parker
Jan 1, 2008·Seizure : the Journal of the British Epilepsy Association·Chunfu ChenPingping Zuo
Dec 10, 2014·European Journal of Nuclear Medicine and Molecular Imaging·S LavisseP Hantraye
May 23, 2012·Glia·Sriram VennetiClayton A Wiley
Jun 22, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Junchao TongStephen J Kish
Dec 16, 2017·Nuclear Medicine and Molecular Imaging·Md Maqusood AlamSang-Yoon Lee
Sep 18, 2009·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Qi GuoRoger N Gunn
Jan 4, 2006·Pharmacology, Biochemistry, and Behavior·Marc VerleyeJean-Marie Gillardin

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