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

Brain Res Bull. 1987 Jan;18(1):49-61. doi: 10.1016/0361-9230(87)90033-5.

Abstract

The peripheral-type benzodiazepine binding site, erstwhile characterized in the rodent and feline brain, has now been characterized in post-mortem human brain using [3H]PK 11195. The kinetics and pharmacological properties of the binding of this ligand are similar to peripheral-type benzodiazepine binding sites elsewhere. The potency of RO5-4864 for this site in human brain is close to that seen in ruminant and carnivore tissues but considerably lower than in rodent tissues. The regional distribution of these binding sites would suggest a neuronal rather than a glial localization. [3H]PK 11195 bound in a similar fashion to slide-mounted sections of human brain, thus allowing quantitative studies of the regional distribution of peripheral-type benzodiazepine binding sites to be made. The binding sites were distributed heterogeneously, but were restricted to the grey matter. Highest densities of binding sites were found in forebrain structures. The localization was not limited to any functional system, nor did it resemble any previously described transmitter system. The similarities between peripheral-type benzodiazepine binding sites in 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Autoradiography
  • Benzodiazepinones / metabolism
  • Brain / metabolism*
  • Cats
  • Cerebral Cortex / analysis
  • Humans
  • Isoquinolines / metabolism*
  • Radioligand Assay
  • Receptors, GABA-A / metabolism*
  • Subcellular Fractions / analysis

Substances

  • Benzodiazepinones
  • Isoquinolines
  • Receptors, GABA-A
  • 4'-chlorodiazepam
  • PK 11195