Localization of the peripheral-type benzodiazepine binding site to mitochondria of human glioma cells.

Abstract

Subcellular fractionation was performed on human U251 glioblastoma cultures. In all subcellular fractions, the binding of the peripheral benzodiazepine ligand, [3H]PK 11195, correlated with the specific activity of monoamine oxidase (r = 0.95, p less than 0.001) and succinate dehydrogenase (r = 0.93, p less than 0.001), two mitochondrial enzymes. The specific activity of plasma membrane and nuclear markers correlated poorly with the presence of PK 11195 binding sites. These data support the mitochondrion as the primary location of peripheral-type benzodiazepine binding sites (PBBS) in human glioma cells. Mitochondria-rich preparations were then assayed for [3H]Ro5-4964 binding. Six nM [3H]Ro5-4964 failed to specifically bind to human U251 mitochondria, but bound vigorously to mitochondria from rat C6 glioma. These data indicate that the low affinity of Ro5-4864 for PBBS in human glioma cells compared to those in rat is due to interspecies receptor variation rather than impaired drug transport into human cells.

• Authors: J M Olson, W McNeel, A B Young, W R Mancini
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 13 Issue 1 Pg. 35-42 (May 1992) ISSN: 0167-594X [Print] United States
• PMID: 1319474 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Neoplasm
• Isoquinolines
• Receptors, GABA-A
• Tritium
• Succinate Dehydrogenase
• Monoamine Oxidase
• Alkaline Phosphatase
• PK 11195

Topics

• Alkaline Phosphatase (analysis, metabolism)
• Animals
• Cell Line
• DNA, Neoplasm (analysis)
• Glioma (metabolism)
• Humans
• Isoquinolines (metabolism)
• Mitochondria (metabolism)
• Monoamine Oxidase (analysis, metabolism)
• Rats
• Receptors, GABA-A (analysis, metabolism)
• Succinate Dehydrogenase (analysis, metabolism)
• Tritium