Mj. Woods et al., 2 CELLULAR AND SUBCELLULAR LOCATIONS FOR THE PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR IN RAT-LIVER, Biochemical pharmacology, 51(10), 1996, pp. 1283-1292
Determination of ligand binding properties of the peripheral benzodiaz
epine receptor (PBBS) in liver, in hepatocytes, and in nonparenchymal
cells demonstrated the presence of receptor-specific high-affinity bin
ding in both hepatocyte and nonhepatocyte cells. Density gradient cent
rifugation showed that the high-affinity receptor in hepatocytes was l
ocalised to mitochondria, whereas in nonhepatocytes it was not mitocho
ndrial, but with a possible biliary epithelial cell plasma-membrane lo
cation. Both receptors showed the peripheraltype specific high affinit
y binding of PK 11195 and Ro5 4864 and could be photolabelled as 18 kD
a proteins with [H-3]PK 14105. Immunocytochemistry showed the presence
of acyl-CoA binding protein, a putative endogenous ligand for the rec
eptor, in both cell locations. Some other properties of the PBBS were
investigated in liver. Diphosphatidyl glycerol had a strong inhibitory
effect on receptor binding in both liver and adrenal, with Ro5 4864 m
ore sensitive to inhibition than PK 11195. However, whereas soybean li
pid and phosphatidyl serine increased the binding of both ligands to a
drenal receptor, these lipids had no effecton liver, suggesting that l
iver PBBS may differ from the well-characterised adrenal PBBS in some
of its protein conformation. Modulators of mitochondrial respiration t
hat also influence intermembrane contact site formation were found to
elicit no marked stimulatory or inhibitory effects on PBBS ligand bind
ing in liver, a result also found for adrenal mitochondria, suggesting
that the extent of contact site formation does not influence ligand b
inding and that the hepatocyte receptor may not play a role in regulat
ing mitochondrial respiration. These two cellular and subcellular loca
tions of the PBBS in liver and the different effect of phospholipids c
ompared to other peripheral tissues may be important for the role(s) o
f PBBS in liver and also for the multiple roles ascribed to the recept
or and to peripheral-type benzodiazepine ligands.