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The role of benzodiazepine receptors in the induction of differentiation of HL-60 leukemia cells by benzodiazepines and purines by Kimiko Ishiguro; William C. Taft; Robert J. DeLorenzo; Alan C. Sartorelli is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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A series of benzodiazepines was evaluated for their capacity to induce the differentiation of HL-60 acute promyelocytic leukemia cells. Benzodiazepines were effective initiators of maturation in the concentration range of 50 to 150 pM. The possible involvement of benzodiazepine receptors in mediating the differentiation induced by these agents was investigated. The presence of high affinity, peripheral type benzodiazepine binding sites (KD = 7.3 nM, TB = 14.5 pmol/mg protein with Ro5-4864) was demonstrated in HL-60 membranes. The occupancy of peripheral type high affinity benzodiazepine receptors by various benzodiazepines showed some correlation (r = 0.76) with their differentiation-inducing capabilities, but binding potencies were 1,000fold higher than the concentrations required to produce differentiation. A class of benzodiazepine receptors with lower binding affinity was also detected in HL-60 membranes (KD = 28.6 pM; TB = 199 prnollmg protein with diazepam). A higher level of correlation (r = 0.88) was demonstrated between benzodiazepine occupancy of these lower affinity receptors and the capacity to induce maturation. Significantly, benzodiazepine concentrations needed for l

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Author

Kimiko Ishiguro; William C. Taft; Robert J. DeLorenzo; Alan C. Sartorelli

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0021-9541)

Published

1987

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)