Dipeptide transport across rat alveolar epithelial cell monolayers.
The transepithelial transport and metabolism of two model peptides, glycyl-D-phenylalanine (Gly-D-Phe) and glycyl-L-phenylalanine (Gly-L-Phe), across primary cultured monolayers of rat alveolar epithelial cells were studied. These tight monolayers (> 2000 omega-cm2) exhibited type I pneumocyte morphological and phenotypic characteristics. A reverse-phase HPLC was used to monitor the appearance of parent dipeptides and their metabolites (D- or L-Phe) in the receiver fluid. The apparent permeability coefficient (Papp) for Gly-D-Phe was about 1.6 x 10(-7) cm/sec at both 1 and 10 mM and in both the apical-to-basolateral (AB) and the basolateral-to-apical (BA) directions. In contrast, the Papp of Gly-L-Phe at 1 mM was about two times higher than that at 10 mM in the AB direction. The Papp of Gly-L-Phe in the BA direction at either concentration was about the same (about 1.4 x 10(-7) cm/sec). Whereas no metabolite was detected during Gly-D-Phe transport, the proportions of a metabolite, L-Phe, observed at 4 hr in the basolateral receiver fluid for 1 and 10 mM apical donor Gly-L-Phe accounted for 83 and 77% of the estimated total Gly-L-Phe (i.e., L-Phe+Gly-L-Phe), respectively. The corresponding values in the BA direction were 40 and 19% of the estimated total Gly-L-Phe in the apical receiver reservoir. Metabolism of Gly-L-Phe was significantly reduced in the presence of 3 microM actinonin (an inhibitor relatively specific for aminopeptides M) in the apical but not the basolateral fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Morimoto
K
K
Department of Pharmaceutical Sciences, University of Southern California, Los Angeles 90033.
Yamahara
H
H
Lee
V H
VH
Kim
K J
KJ
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004151:Dipeptides / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004151:Dipeptides