Cortical benzodiazepine receptor binding in a rabbit model of hepatic encephalopathy: the effect of Triton X-100 on receptor solubilization.
Increased benzodiazepine (BZ) receptor density has been reported in brains of rabbits with hepatic encephalopathy (HE) due to galactosamine (GalN)-induced fulminant hepatic failure (FHF). These data were generated using detergent-Triton X-100-treated neural membranes. While performing further studies it was noted that the increase in BZ receptor density was not demonstrable when Triton X-100 preparation was not employed. Accordingly the binding of [3H] flunitrazepam, a BZ ligand, to neural membranes from cortices of normal rabbits and rabbits with HE due to (GalN)-induced FHF was studied with and without detergent preparation. Scatchard plot analysis of the binding data indicated that when no detergent was employed, the apparent affinity and density of BZ receptors were similar for control membranes and membranes from animals in HE. BZ receptors from animals in HE were shown to be more resistant to solubilization by Triton than control membranes. These findings (a) afford a potential explanation for the apparent increase in density of BZ receptors in this model when Triton treatment of neural membranes is utilized and (b) suggest that recent evidence for increased GABAergic tone in the syndrome of HE is not dependent on an increased density of BZ receptors.
Rössle
M
M
Liver Diseases Section, NIDDK, Bethesda, Maryland 20892.
Mullen
K D
KD
Jones
E A
EA
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005445:Flunitrazepam / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012995:Solubility; D013347:Subcellular Fractions / Q000378:metabolism
D008565:Membrane Proteins; D011963:Receptors, GABA-A; D011092:Polyethylene Glycols; D005445:Flunitrazepam; D017830:Octoxynol