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Brain capillary endothelial cells form the blood-brain barrier (BBB). They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins mediates amino acid (AA) homeostasis in the brain. The existence of two facilitative transporters for neutral amino acids (NAAs) on both membranes provides the brain access to essential AAs. Four [Na.sup.+]-dependent transporters of NAA exist in the abluminal membranes of the BBB. Together these systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and from there into circulation. The presence of [Na.sup.+]-dependent carriers on the abluminal membrane provides a mechanism by which NAA concentrations in the ECF of brain are maintained at ~10% those of the plasma. Also present on the abluminal membrane are at least three [Na.sup.+]-dependent systems transporting acidic AAs (EAAT) and a [Na.sup.+]-dependent system transporting glutamine (N). Facilitative carriers for glutamine and glutamate are found only in the luminal membrane of the BBB. This organization promotes the net removal of acidic- and nitrogen-rich AAs from the brain and accounts for the low level of glutamate penetration into the central nervous system. The presence of a [gamma]-glutamyl cycle at the luminal membrane and [Na.sup.+]-dependent AA transporters at the abluminal membrane may serve to modulate movement of AAs from blood to the brain. The [gamma]-glutamyl cycle is expected to generate pyroglutamate (synonymous with oxyproline) within the endothelial cells. Pyroglutamate stimulates secondary active AA transporters at the abluminal membrane, thereby reducing the net influx of AAs to the brain. It is now clear that BBB participates in the active regulation of the AA content of the brain. KEY WORDS: * brain capillaries * endothelial cells * polarity * sodium dependent transport * facilitative transport

Liver 7-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver [Gamma]-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver [Gamma]-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 [+ or -] 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks [Gamma]-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver [Gamma]-cystathionase during lactation. KEY WORDS: L-cysteine; glutathione; lactating mammary gland; L-cystathionine; rats

To study the redistribution of amino acids to the mammary gland during lactation we used lactating and virgin rats fed liquid diets. Virgin rats were divided in two groups: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats), and the other virgin group was fed the normal liquid diet (control). The hepatic availability of amino acids was significantly higher in the lactating rats than in the other two groups, but the uptake and fractional extraction of amino acids by the liver were lower in lactating rats than in the high protein-fed virgin controls. When primary hepatocyte cultures were used, the uptake of 2-amino-[1-14C]isobutyric acid (AIB) and the activity of system A were found to be significantly higher in the hepatocytes from virgin rats fed the high protein diet than in those obtained from the lactating and control virgin groups. No difference was observed between the control virgin rats and the lactating rats. The kinetics of AIB showed that the [V.sub.max]/[K.sub.m] ratio was significantly lower in hepatocytes from lactating rats than in those from the high protein diet-fed virgin rats. Addition of prolactin to the incubation medium decreased the uptake of AIB in hepatocytes from both groups of virgin rats. Moreover, uptake of AIB was greater in bromocriptine-treated lactating rats and in lactating rats that had had their pups removed for the preceding 24 h compared with values for the lactating rats. These data suggest that liver amino acid uptake is decreased during lactation, redistributing these amino acids from the liver to the lactating mammary gland, and that prolactin is a potential signal for this intertissue flux of amino acids. INDEXING KEY WORDS: liver; lactation; prolactin; amino acid uptake; rats