TARGETED DELIVERY OF A SUBSTRATE FOR P-GLYCOPROTEIN TO RENAL CYSTS IN-VITRO

Bodipy-verapamil has been tested as a fluorescent substrate for P-glyc oprotein-mediated transepithelial secretion in MDCK-CSA epithelia. Net transepithelial secretion (J(net)) of [H-3]vinblastine from basal-to- apical surfaces of monolayer epithelia is inhibited by taxotere, verap amil and Bodipy-verapamil primarily by a reduction in basal to apical vinblastine (J(b-a)) transport. Bodipy-verapamil is itself subject to transepithelial net secretion by MDCK-CSA epithelia; at 5 mu M a J(net ) 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, Bodi py-verapamil is accumulated within the cyst lumen showing that epithel ial P-glycoprotein function may be used to target substrates to renal cysts.