A study of the mechanism of transport of diphenylhydantoin in the rat submaxillary gland in vitro.
In vitro studies performed on rat submaxillary gland slices with diphenylhydantoin (6 X 10(-6) M) showed that variations of extracellular pH (pHe) had no significant effects on uptake and only slight effects on efflux (lowering the pHe slightly decreased efflux rates, whereas increasing pHe slightly increased efflux rates). Increasing diphenylhydantoin concentration significantly decreased uptake and slightly increased the rate of efflux. Uptake of 14C-diphenylhydantoin was significantly decreased when compared to control conditions (pH 7.40, 37 degrees C, 100% O2 aeration, 6 X 10(-6) M) by the following alterations: aeration of the incubation medium with N2 instead of O2, decrease of bath temperature from 37 degrees C to 5 degrees C and addition of the following metabolic inhibitors: iodoacetic acid (10(-3)M), 2,4-dinitrophenol (10(-3)M) and cyanide (10(-3)M). Probenecid (10(-3)M) had no significant effect on diphenylhydantoin uptake when compared to control values. No evidence of salivary biotransformation of diphenylhydantoin was seen in the in vitro system using thin-layer chromatography. These in vitro data suggest an active transport process that is concentration-dependent with a possible saturable binding site on the membrane or in the interior of the cell.