Regional brain indoleamine metabolism following chronic portacaval anastomosis in the rat.

— Four weeks after portacaval anastomosis in the rat. a profound change in the pattern of the plasma neutral ammo acids occurred. These changes were accompanied by marked regional changes in brain trvptophan. 5-HT (5-hydroxytryptamine) and 5-HIAA (5-hydroxyindoleacetic acid). Tryptophan was elevated in all the regions studied as was 5-HIAA. 5-Hydroxytryptamine was significantly elevated only in midbrain and medulla pons. A small but significant increase in free trvptophan concentration in plasma was seen in rats following portacaval anastomosis, but this elevation was insufficient in magnitude to account for thc changes in brain trvptophan. Administration of a solution containing equimolar concentrations of the three branched-chain amino acids, leucine. isoleucine and valine. caused a decrease in brain indoles towards normal levels. These results suggest that the altered plasma neutral amino acid pattern which accompanies portacaval anastomosis and its effect on competitive amino acid transport across the blood brain barrier is an important factor contributing to the raised levels of indoles in brain under these circumstances. The relationship of these results to the recently reported use of amino acid infusions in the treatment of hepatic encephalopathy is discussed.