Targeted delivery of a substrate for P-glycoprotein to renal cysts in vitro.

Abstract

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.

• Authors: N L Simmons, J Hunter, M A Jepson
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1237 Issue 1 Pg. 31-6 (Jul 06 1995) ISSN: 0006-3002 [Print] Netherlands
• PMID: 7619839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Drug Carriers
• Tritium
• Bodipy-verapamil
• Vinblastine
• Verapamil
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Animals
• Biological Transport
• Cell Line
• Drug Carriers
• Kidney Diseases, Cystic (drug therapy, metabolism)
• Microscopy, Confocal
• Paclitaxel (pharmacology)
• Tritium
• Verapamil (analogs & derivatives, pharmacology)
• Vinblastine (metabolism)