INHIBITORS OF CHOLINE TRANSPORT IN ALVEOLAR TYPE-II EPITHELIAL-CELLS

Isolated alveolar type II epithelial cells (granular pneumocytes) from rat lung accumulate free choline against a concentration gradient by an energy-dependent saturable transport process with apparent K(m) app roximately 18-mu-M. In order to evaluate the structural requirements f or choline transport by these cells, the inhibition of the initial rat e of cellular uptake of [H-3]choline (5-mu-M) by its analogue was meas ured. There was no significant inhibition of substrate uptake by analo gues lacking an amino group while the presence of a quaternary nitroge n was most effective. N,N'-dimethylethanolamine (apparent K(i), 7-mu-M ) and n-decylcholine (apparent K(i), 0.5-mu-M) were potent competitive inhibitors of choline transport. Substitution of the hydroxyl group i n choline greatly diminished the inhibitory effect; fluorocholine, thi ocholine, betaine, and betaine aldehyde showed little or no inhibition . This requirement for a hydroxyl group raises the possibility of hydr ogen bonding of choline with the transport protein. The choline transp ort system in granular pneumocytes appears to differ from that in syna ptosomes by the lower affinity of the carrier for substrate and for he micholinium-3 and from that in erythrocytes by the role of the hydroxy l in the substrate molecule. The availability of inhibitory analogues for choline transport will facilitate isolation and study of the granu lar pneumocyte choline transport protein.