The effect of sodium taurocholate on the hepatic metabolism of sulfobromophthalein sodium (BSP). The role of bile flow.

The influence of bile salts on the hepatic metabolism of sulfobromophthalein sodium (BSP) was studied in the perfused rat liver. During sodium taurocholate infusions, hepatic uptake of BSP from plasma was increased and appeared to be related to an enhanced transit of BSP from liver into bile. BSP-glutathione conjugation was not affected by the bile salt infusions, although bile salts inhibited the enzyme system in vitro. The major effect of bile salts was to increase the BSP transport maximum (Tm). When sodium taurocholate was infused in saline at a rate of 30 mumoles/hr, both bile flow and the BSP Tm increased, and remained at peak levels of 1.5 +/-0.12 mul/min per g liver and 21 +/-3.0 mug/min per g liver, respectively. In contrast, during saline infusion alone both levels were significantly lower (1.06 +/-0.17 mul/min per g liver and 15.8 +/-4.16 mug/min per g liver, respectively), and both fell progressively after the 2nd hr of perfusion. This decline in bile flow and BSP Tm was associated with a decrease in biliary bile salt excretion and was reversed by adding bile salts to the perfusate. Since the biliary concentration of BSP remained within a narrow range in all experiments, the BSP Tm was primarily determined by the rate of bile flow. Dependence of BSP Tm on the rate of bile production was further confirmed by changing the temperature of the perfusate during a constant infusion of taurocholate. BSP Tm paralleled temperature-induced changes in bile flow irrespective of changes in the level of bile salt excretion. Since the biliary concentration of BSP remained within a narrow range in all experiments, the concentrating capacity for BSP in bile may be the major limiting factor in BSP transport. Thus two independent factors appear to determine the BSP Tm: the bile BSP concentration, and the rate of bile production. Because taurocholate enhanced BSP transport only when it increased bile production, its effect on the BSP Tm appears to be attributable to its choleretic properties.

Mechanism of inhibition of alanine absorption by Na ricinoleate.

The mechanism of inhibition of alanine absorption by Na ricinoleate has been examined in the rabbit intestine. This fatty acid in a concentration of 2--5 mM inhibits alanine absorption in vivo and in vitro. The inhibition is more evident in the jejunum than in the ileum. Strips of ileal mucosa treated with Na ricinoleate gain Na. Sodium ricinoleate inhibits alanine influx across rabbit ileum, even in the presence of a sodium gradient across these cells. The results suggest that the main action of Na ricinoleate is on the alanine-transport system at the brush-border membrane. The fatty acid may also inhibit amino acid absorption by increasing intestinal cell Na concentration, which results in a decreased Na gradient across the brush-border membrane.

Effect of chronic ethanol consumption on leucine absorption in the rat small intestine.

Intestinal absorption of leucine was measured in vivo in rats given ethanol for 7 weeks either through a liquid diet or through drinking water and the results were compared with pair-fed and ad libitum-fed control rats. Total leucine absorption by the entire intestine was not inhibited by ethanol but specific absorption per dry weight of mucosa was increased in the ethanol-fed rats. The intestine of the ethanol-fed rats was shorter and thinner then the ad libitum control rats but its absorptive capacity was maintained by functional adaptation probably by a mechanism similar to that which occurs with semistarvation.

Effect of ethanol on amino acid absorption across in vivo rat intestine.

The acute effect of ethanol on amino acid absorption across the in vivo rat intestine was studied using single-pass continuous perfusion and recirculation techniques. The single-pass steady-state perfusion was used to examine the effect on the entire small intestine and recirculation perfusion to examine the effect on short intestinal segments and to limit ethanol absorption. Unlike the in vitro findings of other investigators, ethanol does not cause inhibition of net amino acid absorption in vivo unless the alcohol is perfused in 2 M or higher concentrations. The inhibition that is observed at these concentrations is very likely due to severe injury and shedding of intestinal cells as evidenced by an increased recovery of DNA in the perfusates. The findings suggest that acute ethanol administration, in concentrations that are comparable to those found in the upper intestines of humans after the ingestion of moderate doses of alcohol, does not have a prominent effect on amino acid absorption across the in situ rat intestine. Under these conditions, the ethanol inhibition of active absorption is masked by enhanced diffusion of the amino acids across the intestine.