Labelling of peripheral-type benzodiazepine binding sites in human brain with [3H]PK 11195: Anatomical and subcellular distribution

Abstract The peripheral-type benzodiazepine binding site, erstwhile characterized in the rodent and feline brain, has now been characterized in post-mortem human brainusing[ 3 H] PK 11195. The kinetics and pharmacological properties of the binding of this ligand are similar to peripheral-type benzodiazepine binding siteselsewhere. The potency of RO5-4864for this site in human brainis close to that seen in ruminate and carnivore tissues but considerably lower than in rodent tissues. The regional distribution of these binding siteswould suggest a neuronal rather than a glial localization. [ 3 H] PK 11195bound in a similar fashion to slide-mounted sections of human brain, thus allowing quantitative studies of the regional distribution of peripheral-type benzodiazepine binding sitesto be made. The binding siteswere distributed heterogeneously, but were restricted to the grey matter. Highest densities of binding siteswere found in forebrain structures. The localization was not limitedto any functionalsystem, nor did it resemble any previously described transmitter system. The similarities between peripheral-type benzodiazepine binding sitesin human and in feline brain in terms of their pharmacological characteristics and their regional and subcellular distribution suggest that the cat, rather than the rat, may be the better model for studying a possible role for this site in human cerebral function.