RT Journal Article
SR Electronic
T1 Resolving receptor heterogeneity using Fourier-derived affinity spectrum analysis and LIGAND: benzodiazepine receptors in the rat spinal cord.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 842
OP 849
VO 273
IS 2
A1 P A Maguire
A1 J I Mechanick
A1 M F Davies
A1 D M Ellis
A1 D B Meredith
A1 G H Loew
YR 1995
UL http://jpet.aspetjournals.org/content/273/2/842.abstract
AB In the present study, we combined a powerful and novel receptor binding data analysis technique. Fourier-derived affinity spectrum analysis (FASA), with the nonlinear regression analysis program LIGAND to resolve benzodiazepine receptor heterogeneity in rat spinal cord. With FASA, we identified three distinct [3H]Ro15-1788 binding populations: two high-affinity sites (0.4 and 5 nM) for the radioligand and a lower-affinity site (150 nM) that is insensitive to the imidazopyridine alpidem. With the affinities for the radioligand determined with FASA, the Ki values of 13 competing ligands were calculated with LIGAND. All of the ligands studied displayed the highest affinity for site 1 (the highest-affinity [3H]Ro15-1788 binding site), with the exception of AHR 11797. Site 2 had high affinity for Ro15-1788, lower affinity for flunitrazepam and beta-CCM and very low, but measurable, affinity for zolpidem. The alpidem-insensitive binding site, studied in isolation by performing competitive binding assays in the presence of 65 microM alpidem, showed relatively low affinity for all of the ligands studied, and its physiological relevance is not yet known.