Uptake of Amino Acids by Brain Micro vessels Isolated from Rats with Experimental Chronic Renal Failure

Abstract

The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Characteristics of large neutral amino acid‐induced release of preloaded L‐glutamine from rat cerebral capillaries in vitro: Effects of ammonia, hepatic encephalopathy, and γ‐glutamyl transpeptidase inhibitors

“…The observations that both ammonia treatment in vitro and hepatic encephalopathy in vivo potentiated the TRY-stimulated Gln release is consistent with the enhanced TRY and other neutral amino acids uptake into capillaries pretreated with Gln (Cangiano et al, 1983) or ammonia (Cardelli-Cangiano et al, 1984), or derived from rats subjected to different hyperammonemic conditions (Cardelli-Cangiano et al, 1981;Cangiano et al, 1988). Cardelli-Cangiano et al (1984) suggested an indirect mechanism of stimulation by ammonia, i.e., via the synthesis of excess Gln.…”

“…Cardelli-Cangiano et al (1984) suggested an indirect mechanism of stimulation by ammonia, i.e., via the synthesis of excess Gln. However, these authors preincubated the capillaries with ammonia 20 min prior to uptake measurements, which favored de novo synthesis.…”

“…Increased uptake of TRY and other large neutral amino acids (LNAA) across the cerebral capillaries, which form the blood-brain barrier (BBB), has been postulated to occur in exchange of glutamine (Gln), whose levels measured in the whole brain (Butterworth et al, 1987;Hawkins et al, 1987;Bates et al, 1989), but also in the isolated cerebral capillaries (Cardelli-Cangiano et al, 1981;Cangiano et al, 1988), markedly increase in hyperammonemic conditions. In vitro studies have demon-strated that preloading of cerebral capillaries with L-Gln increases their ability to take up TRY and other LNAA, which was interpreted to manifest an exchange via the L-transport system (Cangiano et al, 1983).…”

Brain amino acid abnormalities in kidney disease and diabetes mellitus

“…In the plasma of uremic patients, elevated concentrations of PHE were found [22], which may be attributed to an abolished renal uptake of PHE in the uremic state [23] and a defective hydroxylation of PHE resulting from partial inhibition of the enzyme phenylalanine hydroxylase [24,25]. In addition, a significantly greater uptake of PHE was shown in brain microvessels isolated from rats with chronic uremia [26]. In keeping with these findings, the brain tissue of the deceased with advanced renal disease in our study exhibited an elevated concentration of PHE.…”

CHARACTERIZATION OF CATIONIC AMINO ACID TRANSPORT SYSTEMS IN RAT ERYTHROCYTES: LACK OF EFFECT OF URAEMIA ON l‐ARGININE INFLUX

“…The present finding that rat plasma l-arginine concentrations are not altered following partial nephrectomy is consistent with previous reports. 15,33,34 In a rat experimental model of renal mass reduction, hypertrophy of the proximal tubule in the remnant nephrons resulted in an increase in l-arginine synthesis per nephron. 11 It is also possible that extrarenal tissues maintain normal plasma levels of l-arginine.…”