RT Journal Article
SR Electronic
T1 Enhancement of diphenylhydantoin binding by lipid extraction.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 579
OP 585
VO 196
IS 3
A1 Goldberg, M A
A1 Todoroff, T
YR 1976
UL http://jpet.aspetjournals.org/content/196/3/579.abstract
AB The binding of diphenylhydantoin-14C (DPH-14C) to several purified proteins and a number of tissue fractions from rats and rabbits has been studied by ultrafiltration and dynamic dialysis. In all cases the extent of binding correlated very closely with the protein concentration of the fraction investigated. Although binding to purified proteins varied considerably, binding to whole brain, subcellular fractions, liver, heart and kidney were identical. Skeletal muscle bound significantly less than other tissues. When brain homogenates were extracted with acetone or chloroform-methanol (2:1), the insoluble residue bound considerably greater amounts of DPH-14C per milligram of protein. Binding decreased after incubation with a proteolytic enzyme, but was not influenced by the addition of cations, ethylenediamine tetraacetic acid or ouabain. DPH-3H binding was constant over a large range of DPH concentrations (1 X 10(-10) to 2 X 10(-4)M) with no evidence for saturable or high affinity binding sites. It is suggested that tissue protein binding plays a role in the delayed attainment of adequate serum levels and the pharmacologic action of DPH.