Transport of a series of D-phenylalanine-glycine hexapeptides across rat alveolar epithelia in vitro.
The effect of lipophilicity on the absorption of peptides from the lungs was investigated. D-phenylalanine (F)-glycine (G) hexapeptides were synthesised to differ, predominantly, only in their lipophilicity. Rat alveolar type II cells were isolated and cultured on plastic, or polycarbonate filters; by day 6 they had de-differentiated to an alveolar type I-like epithelium. The permeability of the monolayers to the hexapeptides was determined. The hexapeptides were metabolically and chemically stable for greater than 24h in the presence of the cells. They did not adhere to the cell culture plastic and were associated only to a low extent with the cell monolayer. The apical to basolateral permeability coefficients for D-F1G5, D-F2G4, and D-F3G3 were 2.19+/-0.53, 1.75+/-0.42 and 2.20+/-0.56 x 10(-7) cm s(-1) respectively. The permeability of the monolayers to D-F1G5 and D-F2G4 was concentration and direction independent, however for D-F3G3 the monolayer was more permeable in the basolateral to apical direction. There was no correlation between the lipophilicity of the hexapeptides and permeability coefficients: other physicochemical parameters did not predict hexapeptide transport. Lipophilicity does not appear to control the transport of hexapeptides across the alveolar epithelium probably as a consequence of the peptides being transported via the paracellular route.
Evans
J P
JP
Welsh School of Pharmacy, University of Wales, Cathays Park, Cardiff, UK.
Tudball
N
N
Dickinson
P A
PA
Farr
S J
SJ
Kellaway
I W
IW
D000465:Algorithms; D000818:Animals; D001692:Biological Transport; D002470:Cell Survival; D002478:Cells, Cultured; D004355:Drug Stability; D004847:Epithelial Cells / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry*; D008297:Male; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats
D009842:Oligopeptides; D010649:Phenylalanine; D005998:Glycine