Release of osmolytes from perfused rat liver on perivascular nerve stimulation: alpha-adrenergic control of osmolyte efflux from parenchymal and nonparenchymal liver cells

The effects of perivascular nerve stimulation and phenylephrine on osmolyte release were studied in the intact perfused rat liver and isolated liver p arenchymal cells (PC) and nonparenchymal cells. In the perfused liver, elec trical stimulation of perivascular nerves (20 Hz/2 ms/20 V) led to a phento lamine-sensitive increase of cell hydration by 6.5% +/- 1.2% (n = 3) and a transient phentolamine-sensitive stimulation of taurine and inositol, but n ot betaine, release. These nerve effects were mimicked by phenylephrine, bu t not prostaglandin Fz,, and were not affected by sodium nitroprusside (SNP ) or ibuprofen. Nerve stimulation-induced taurine, but not inositol, releas e was inhibited by 4,4 '-di-isothiocyanatostilbene-2,2'-disulphonic acid (D IDS) (50 mu mol/L), Single-cell fluorescence studies with isolated liver PC , Kupffer cells (KC), sinusoidal endothelial cells (SEC), and hepatic stell ate cells (HSC) revealed that phenylephrine induced an increase in cytosoli c free Ca2+ only in PC and HSC, but not in KC and SEC, whereas extracellula r uridine triphosphate (UTP) produced Ca2+ transients/oscillations in all l iver cell types studied. Phenylephrine had no effect on osmolyte release fr om isolated KC and SEC, but increased taurine (but not inositol) release fr om PC and inositol (but not taurine) efflux from HSC. The data suggest that : 1) liver cell hydration and-consecutiveIy-osmolyte content are modulated by hepatic nerves via an alpha-adrenergic mechanism, which does not involve eicosanoids or hemodynamic changes; 2) that PC and HSC are the primary tar gets for nerve-dependent alpha-adrenergic activation, whereas 3) KC and SEC probably do not express alpha-adrenoceptors coupled to Ca2+ mobilization o r osmolyte efflux.