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 wa s investigated. D-phenylalanine (F)-glycine (G) hexapeptides were synthesis ed 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 24 h in the presence of the cells. They did not adhere to the cell culture plas tic and were associated only to a low extent with the cell monolayer. The a pical to basolateral permeability coefficients for D-F(1)G(5) D-F(2)G(4), D -F(3)G(3) were 2.19+/-0.53, 1.75+/-0.42 and 2.20+/-0.56 x 10(-7) cm s(-1) r espectively. The permeability of the monolayers to D-F(1)G(5) and D-F(2)G(4 ) was concentration and direction independent, however for D-F(3)G(3) the m onolayer was more permeable in the basolateral to apical direction. There w as no correlation between the lipophilicity of the hexapeptides and permeab ility coefficients: other physicochemical parameters did not predict hexape ptide transport. Lipophilicity does not appear to control the transport of hexapeptides across the alveolar epithelium probably as a consequence of th e peptides being transported via the paracellular route.