A P-glycoprotein homologue in Manduca sexta: Steps toward cDNA cloning.

Abstract

One of the proposed natural functions of P-glycoprotein is to provide protection against xenobiotics; this could be accomplished by expression of the efflux pump in excretory and blood-organ barrier tissues to prevent the penetration of foreign toxins to sensitive organs. Involvement of Pgp in the mouse blood-brain barrier to the pesticide ivermectin has been convincingiy demonstrated (Schinkel et al., 1994). Demonstrating that a P-glycoprotein homologue is a factor in the nicotine resistance of Manduca sexta would provide substantial support for the xenobiotic theory. It would also be the first demonstration of the involvement of Pgp in a natural ecological relationship; thus far Pgp has only been implicated in "unnatural" situations where there is a man-made toxic insult with pollutants, pesticides or cytotoxic drugs. Ongoing work in our laboratory has shown that alkaloid transport by Manduca Malpighian tubules behaves pharmacologically like Pgp drug transport. Corroboration of this physiological work by molecular cloning of the P-glycoprotein homologue from Manduca is the long-term goal of this project. Subsequent experiments were intended to identify the problems associated with the cloning project. (Abstract shortened by UMI.)