Further studies on the high-affinity binding of 3H-alaproclate to membranes from rat liver and some other tissues.

The high affinity binding of 3H-alaproclate to membranes in liver homogenates from naive rats and those treated with phenobarbital sodium, 75 mg/kg intraperitoneally, alaproclate hydrochloride, 40 mg/kg intraperitoneally proadifen hydrochloride, 40 mg/kg intraperitoneally once daily for 7 days and killed 24 hr after the last injection was examined. The treatment increased the normal number of alaproclate binding sites (Bmax: 1.1 nmol/g tissue, KD: 0.6 nM) by factors of about 10, 4 and 6, respectively. About 80% of the binding was localized to the microsomal fraction in both normal and phenobarbital treated rats. Ninety % of the alaproclate displaceable binding in a microsomal preparation of the normal liver was inhibited by low (nM) concentrations of proadifen whereas only about 20% in the liver preparations from phenobarbital treated rats was inhibited by low concentrations of proadifen. Thus, the main part of the induced binding sites was insensitive to proadifen. The same was found for the alaproclate and proadifen-induced alaproclate binding sites. The stereoselectivity of alaproclate enantiomers for binding to the normal and the induced binding sites was different: the S-(-) form was 100 times more potent than the R-(+)- enantiomer in inhibiting binding of racemic alaproclate to the normal sites, whereas the latter form was 3 times more potent than the former in inhibiting the binding to the phenobarbital-induced proadifen insensitive binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)