Organic cation transport in rabbit alveolar epithelial cell monolayers

Citation
J. Shen et al., Organic cation transport in rabbit alveolar epithelial cell monolayers, PHARM RES, 16(8), 1999, pp. 1280-1287
Citations number
30
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACEUTICAL RESEARCH
ISSN journal
07248741 → ACNP
Volume
16
Issue
8
Year of publication
1999
Pages
1280 - 1287
Database
ISI
SICI code
0724-8741(199908)16:8<1280:OCTIRA>2.0.ZU;2-F
Abstract
Purpose. To characterize organic cation (OC) transport in primary cultured rabbit alveolar epithelial cell monolayers, using [C-14]-guanidine as a mod el substrate. Methods. Type II alveolar epithelial cells from the rabbit lung were isolat ed by elastase digestion and cultured on permeable filters precoated with f ibronectin and collagen. Uptake and transport studies of [C-14]-guanidine w ere conducted in cell monolayers of 5 to 6 days in culture. Results. The cultured alveolar epithelial cell monolayers exhibited the cha racteristics of a tight barrier. [C-14]-Guanidine uptake was temperature de pendent, saturable, and inhibited by OC compounds such as amiloride, cimeti dine, clonidine, procainamide, propranolol, tetraethylammonium, and verapam il. Apical guanidine uptake (K-m = 129 +/- 41 mu M, V-max = 718 +/- 72 pmol /mg protein/5 min) was kinetically different from basolateral uptake (K-m = 580 +/- 125 mu M, V-max = 1,600 +/- 160 pmol/mg protein/5 min). [C-14]-Gua nidine transport across the alveolar epithelial cell monolayer in the apica l to basolateral direction revealed a permeability coefficient (P-app) of ( 7.3 +/- 0.4) X 10(-7) cm/sec, about seven times higher than that for the pa racellular marker [C-14]-mannitol. Conclusions. Our findings are consistent with the existence of carrier-medi ated OC transport in cultured rabbit alveolar epithelial cells.