Release of osmolytes induced by phagocytosis and hormones in rat liver.
Betaine, taurine, and inositol participate as osmolytes in liver cell volume homeostasis and interfere with cell function. In this study we investigated whether osmolytes are also released from the intact liver independent of osmolarity changes. In the perfused rat liver, phagocytosis of carbon particles led to a four- to fivefold stimulation of taurine efflux into the effluent perfusate above basal release rates. This taurine release was inhibited by 70-80% by the anion exchange inhibitor DIDS or by pretreatment of the rats with gadolinium chloride. Administration of vasopressin, cAMP, extracellular 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 endothelial 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 measurements revealed an increase of intracellular calcium concentration in response to vasopressin and glucagon in parenchymal cells and sinusoidal endothelial cells but not in Kupffer cells and hepatic stellate cells. The data show that Kupffer cells release osmolytes during phagocytosis via DIDS-sensitive anion channels. This mechanism may be used to compensate for the increase in cell volume induced by the ingestion of phagocytosable material. The physiological significance of hormone-induced osmolyte release remains to be evaluated.
Wettstein
M
M
Clinic for Gastroenterology, Hepatology, and Infectious Disease, Heinrich Heine University, 40255 Düsseldorf, Germany. wettstein@med.uni-duesseldorf.de
Peters-Regehr
T
T
Kubitz
R
R
Fischer
R
R
Holneicher
C
C
Mönnighoff
I
I
Häussinger
D
D
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001622:Betaine / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology; D014882:Water-Electrolyte Balance
D006728:Hormones; D014667:Vasopressins; D013654:Taurine; D001622:Betaine; D000255:Adenosine Triphosphate; D005934:Glucagon; D005682:Gadolinium; D000242:Cyclic AMP; C038958:gadolinium chloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium