Lithium absorption by the rabbit gall-bladder.
Lithium (Li+) absorption across the low-resistance epithelium of the rabbit gall-bladder was studied in order to elucidate possible routes and mechanisms of Li+ transfer. Li+ at a concentration of 0.4 mM in both mucosal and serosal media did not affect isosmotic mucosa-to-serosa fluid absorption. At this low concentration net mucosa-to-serosa Li+ absorption was insignificant when the ambient Na+ concentration was 115 mM, although the gall-bladder had a significant Li+ permeability (2.7 X 10(-5) cm s-1) and a significant mucosa-to-serosa Li+ gradient developed as a result of fluid absorption. Net Li+ absorption was induced at reduced mucosal Na+ concentrations (by lowering the Na+ concentration down to 50 mM with or without substitution with sucrose, or by adding sucrose to the mucosal medium). This Li+ absorption occurred even in the absence of a mucosa-to-serosa Li+ gradient. Na+ and Li+ absorptions occurring at 50 mM Na+ were inhibited to the same degree by mucosal 1 mM amiloride. Substitution of 5-50 mM (44%) Na+ by Li+ in the external medium dose-dependently depressed Na+ absorption by up to 76%, while substitution by 50 mM choline had no significant effect. Li+ inhibition of Na+ absorption was elicited from the mucosal side and was not accounted for by compensatory Li+ absorption; water and Na+ absorption rates decreased nearly in parallel. The effects of 0.4 mM amiloride and of substitution with 20 mM Li+ were only partly additive. It is concluded that Li+ absorption in the rabbit gall-bladder cannot be explained by passive (paracellular) transport, but must be the result of transcellular, active transport. Both at low and at high concentrations Li+ may enter the cell via an Na+/H+ exchanger in the apical cell membrane. At high concentrations Li+ may inhibit Na+ absorption by interference with the exchange mechanism and/or via effects at the cytoplasmic level. The Li+ transfer mechanism across the basolateral cell membrane remains unknown.
Hansen
C P
CP
Institute of Experimental Medicine, Panum Institute, University of Copenhagen, Denmark.
Holstein-Rathlou
N H
NH
Skøtt
O
O
Leyssac
P P
PP
Frederiksen
O
O
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000378:metabolism*; D008094:Lithium / Q000493:pharmacokinetics*; D009092:Mucous Membrane / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
D002034:Bumetanide; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D002794:Choline