Evidence for extensive and non-specific translocation of oligopeptides across plasma membranes of mammalian cells.
After exposure of bovine aortic endothelial cells to various small peptides (tetra- to undeca-mer), extensive transport of the peptides across the plasma membrane was observed in the concentration range 10(-7) to 10(-2) M. The observed transport events, which contradict the generally anticipated poor permeability of peptides across plasma membranes, exhibited high complexity and showed no saturability up to a concentration of 10(-2) M. Evidence was found for the involvement of mdrp-like transporters as well as of energy-independent facilitated diffusion events. The peptide levels within the cells approximated those of the incubation solution within 30 min, indicating high capacity and velocity for the involved transport processes. Correspondingly, preloaded cells exported about 80% of the internalized peptide within 5 min at 37 degrees C. Analogous results were found after peptide exposure to several other mammalian cell types, indicating a more general importance of the transport phenomena described here. Our findings contradict the prevailing opinion that the often observed lack of activity of externally administered peptides against their targets within intact cells is accounted for primarily by poor cellular uptake and point to export processes counteracting the uptake to be more important in this context.
Oehlke
J
J
Institute of Molecular Pharmacology, Berlin, Germany. bienert@fmp-berlin.de
Beyermann
M
M
Wiesner
B
B
Melzig
M
M
Berger
H
H
Krause
E
E
Bienert
M
M
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D007700:Kinetics; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000378:metabolism*
D004745:Enkephalins; D009842:Oligopeptides