No abstract

It has long been established that the absorption of short-chain fatty acids (SCFA) across epithelia stimulates sodium proton exchange. The apically released protons are not available as countercations for the basolateral efflux of SCFA anions and a suitable transport model is lacking. Patch clamp and microelectrode techniques were used to characterize an anion conductance expressed by cultured cells of the sheep and bovine rumen and the sheep omasum and to localize the conductance in the intact tissue. Cells were filled with a Na-gluconate solution and superfused with sodium salts of acetate, propionate, butyrate, or lactate. Reversal potential rose and whole cell current at +100 mV decreased with the size of the anion. Anion-induced currents could be blocked by diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), NPPB (200 μmol l(-1)), or pCMB (1 mmol l(-1)). In patches of bovine ruminal cells, single channels were observed with a conductance for chloride (327 ± 11 pS), acetate (115 ± 8 pS), propionate (102 ± 10 pS), butyrate (81 ± 2 pS), and gluconate (44 ± 3 pS). Channels expressed by sheep rumen and omasum were similar. Microelectrode experiments suggest basolateral localization. In conclusion, forestomach epithelia express basolateral maxi-anion channels with a permeability sequence of chloride > acetate > propionate > butyrate. SCFA absorption may resemble functionally coupled transport of NaCl, with the Na(+)/K(+)-ATPase driving the basolateral efflux of the anion through a channel. Since protons are apically extruded, the model accurately predicts that influx of buffers with saliva is essential for the pH homeostasis of the ruminant forestomach.

No abstract

Apoptotic cell death is common in the inflamed gastric mucosa, but its role in the regulation of cell homeostasis in normal gastric mucosa is unknown. We investigated the expression of CD95, Bcl-2, and Bax and their roles in the regulation of apoptosis in normal rat gastric mucosa and in cultures of highly enriched rat chief and parietal cells by immunostaining, Western blotting, and FACS. In intact tissue CD95, Bcl-2, and Bax were localized predominantly in the glandular base region in chief cells. In freshly isolated cells, expression of CD95, Bcl-2, and Bax was much more pronounced in chief cells than in parietal cells. A lower intracellular Bcl-2/Bax ratio suggesting a higher susceptibility to apoptosis was noticed in chief rather than in parietal cells. In extended cultures of parietal and chief cells, Bax expression was upregulated and Bcl-2 expression was downregulated. These regulatory changes, presumably caused by in vitro effects, were not associated with an increase in spontaneous apoptosis. Treatment of chief and parietal cells with Fas-ligand induced apoptosis of all CD95 expressing cells. Expression of CD95, Bcl-2, and Bax predominantly in chief cells suggests that in this cell type regulation of apoptosis may differ from that in parietal cells. Binding of FasL with functionally active CD95 receptors on chief and parietal cells may be relevant for induction of apoptosis in inflamed gastric mucosa.

In contrast to EGF and IGF-I, HGF stimulated both growth and differentiation of renal proximal tubular cells, demonstrating the amazing biological potency of this renotropic growth factor. Selective TKIs may be a promising approach to modulate diseases with abnormalities in protein kinase signalling pathways such as renal cell carcinoma.