Release of osmolytes induced by phagocytosis and hormones in rat liver

Betaine, taurine, and inositol participate as osmolytes in liver cell volum e homeostasis and interfere with cell function. In this study we investigat ed whether osmolytes are also released from the intact liver independent of osmolarity changes. In the perfused rat liver, phagocytosis of carbon part icles led to a four- to fivefold stimulation of taurine efflux into the eff luent perfusate above basal release rates. This taurine release was inhibit ed by 70-80% by the anion exchange inhibitor DIDS or by pretreatment of the rats with gadolinium chloride. Administration of vasopressin, cAMP, extrac ellular ATP, and glucagon also increased release of betaine and/or taurine, whereas insulin, extracellular UTP, and adenosine were without effect. In isolated liver cells, it was shown that parenchymal cells and sinusoidal en dothelial cells, but not Kupffer cells and hepatic stellate cells, release osmolytes upon hormone stimulation. This may be caused by a lack of hormone receptor expression in these cells, because single-cell fluorescence measu rements revealed an increase of intracellular calcium concentration in resp onse to vasopressin and glucagon in parenchymal cells and sinusoidal endoth elial cells but not in Kupffer cells and hepatic stellate cells. The data s how that Kupffer cells release osmolytes during phagocytosis via DIDS-sensi tive anion channels. This mechanism may be used to compensate for the incre ase in cell volume induced by the ingestion of phagocytosable material. The physiological significance of hormone-induced osmolyte release remains to be evaluated.