Interaction of P-glycoprotein with a hydrophobic component of rat urine.
The presence of an endogenous P-glycoprotein substrate in rat urine was examined by testing the ability of a hydrophobic extract to reverse multidrug resistance in CHO cells and to inhibit [3H]azidopine photolabelling. The accumulation of several hydrophobic drugs and dyes, known to be transported by P-glycoprotein, was dramatically enhanced in multidrug-resistant CHO cells (CHRC5) by a component contained in a hydrophobic extract prepared from rat urine by octadecyl (C18) reverse phase chromatography. The biological action of this urinary component involves a direct interaction with P-glycoprotein since it blocked photolabelling of the protein with [3H]azidopine. The effective concentration of the substance required to enhance drug accumulation and inhibit photolabelling was similar and within the range of its urinary content. These results suggest that a hydrophobic substance in urine may be an endogenous substrate of kidney P-glycoprotein.
Charuk
J H
JH
Department of Medicine, University of Toronto, Ontario, Canada.
Reithmeier
R A
RA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001386:Azides / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D004095:Dihydropyridines / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D014020:Tissue Extracts / Q000494:pharmacology*; D014556:Urine / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001386:Azides; D004095:Dihydropyridines; D008562:Membrane Glycoproteins; D014020:Tissue Extracts; D014747:Vinblastine; C041130:azidopine; D014700:Verapamil