BETAINE AS AN OSMOLYTE IN RAT-LIVER - METABOLISM AND CELL-TO-CELL INTERACTIONS

Betaine was recently identified as an osmolyte in rat liver macrophage s (Kupffer cells [KCs]) and sinusoidal endothelial cells (SECs). Betai ne interferes with KC functions, such as phagocytosis, cytokine, and p rostaglandin syntheses. As betaine is derived from choline, the presen t study was undertaken to evaluate osmosensitivity and cell heterogene ity of choline metabolism in rat liver. In the perfused rat liver afte r in vivo prelabeling with [C-14]-choline, hypoosmotic stress induced a radioactivity release into the perfusate which was identified as [C- 14]-betaine by highperformance liquid chromatography (HPLC) analysis a nd which was inhibited by the anion exchanger inhibitor 4,4 '-diisothi ocyanostilbene-2,2'-disulfonic acid. Choline metabolism was studied in cultured liver parenchymal cells, (PCs), KCs, and SECs. Choline was t aken up by all but betaine formation from choline was only detectable in PCs and not in KCs and SECs. Betaine formation in PCs was not stimu lated by hyperosmolarity; rather, betaine has a role as an osmolyte in KCs and SECs but is of minor importance in PCs, as evidenced by only minor hyperosmolarity-induced betaine uptake. Thus, liver PCs can prod uce and release betaine derived from choline, and, thereby, possibly s upply the osmolyte important for KC and SEC cell function, This may be another example for cell-to-cell interaction in the liver.