Targeted delivery of a substrate for P-glycoprotein to renal cysts in vitro.
Bodipy-verapamil has been tested as a fluorescent substrate for P-glycoprotein-mediated transepithelial secretion in MDCK-C5A epithelia. Net transepithelial secretion (Jnet) of [3H]vinblastine from basal-to-apical surfaces of monolayer epithelia is inhibited by taxotere, verapamil and Bodipy-verapamil primarily by a reduction in basal to apical vinblastine (Jb-a) transport. Bodipy-verapamil is itself subject to transepithelial net secretion by MDCK-C5A epithelia; at 5 microM a Jnet of -310 +/- 32 nmol cm-2 h-1 (n = 3) was observed. When MDCK-C5A cells are grown to form enclosed cysts in hydrated collagen gel. Bodipy-verapamil is accumulated within the cyst lumen showing that epithelial P-glycoprotein function may be used to target substrates to renal cysts.
Simmons
N L
NL
Department of Physiological Sciences, University of Newcastle upon Tyne, Medical School, UK.
Hunter
J
J
Jepson
M A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D004337:Drug Carriers; D052177:Kidney Diseases, Cystic / Q000188:drug therapy* / Q000378:metabolism; D018613:Microscopy, Confocal; D017239:Paclitaxel / Q000494:pharmacology*; D014316:Tritium; D014700:Verapamil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D014316:Tritium; C071322:Bodipy-verapamil; D014747:Vinblastine; D014700:Verapamil; D017239:Paclitaxel