Kynurenine: penetration to the brain, effect on brain tryptophan and 5-hydroxytryptamine metabolism and binding to plasma albumin [proceedings].

The presence in brain of kynurenine, the first major metabolite of tryptophan on the pathway initiated by the liver enzyme. tryptophan pyrrolase, has recently been reported Since an enzyme capable of forming kynur-enine from tryptophan is present in brain (Gal, 1974; Hayaishi, 1976) it is of interest to study the penetration of kynurenine to the brain following peripheral administration. Peripheral administration of kynurenine has also been reported to reduce rat brain 5HT levels, perhaps via inhibition of tryptophan uptake (Green & Curzon, 1970). (-Kynurenine sulphate (5 mg/kg i.p.) was administered to male Sprague-Dawley rats (weight 200-280 g). As shown in the table kynurenine levels were significantly elevated in plasma 30 min later, and in brain at 30, 60 and 120 min later. These results are in broad agreement with the less detailed findings reported in mice (Gould & Handley, 1978) and in rats (Gal, Young & Sherman, 1978) and confirm that kynur-enine can penetrate to the brain following peripheral administration. Analysis of tryptophan, 5-hydroxy-tryptamine and 5-hydroxy-indoleacetic acid in the brains of the same animals revealed small but non-significant reductions in all three parameters only at 30 and 60 min post kynurenine which is not consistent with the findings of Green & Curzon (1970). Plasma tryptophan was also reduced although not significantly. Ultrafiltration of plasma samples by a technique developed from that of Bloxham, Hutson Table 1 The effect of (-)-kynurenine sulphate administration. i.p., on kynurenine in plasma and brain K! nulrentinelt content Timiie after injection1 of (-)-Plasma Brain ki-nurenine suilphate 5 mig/lkg i.p. (970/) (221 "%) Results as mean + s.d. (no. of animals) (0,, of control). Significantly different from control on 2-tailed 't' test. plasma albumin, since kynurenine was bound to a similar extent. Further data on this binding will be presented, and it is suggested that any effects of kynurenine on brain tryptophan metabolism might be mediated at least in part via effects on tryptophan binding to albumin since the latter is known to affect tryptophan availability to the brain simple apparatus for ultrafiltration of small volumes: application to the measurement of free and albumin-bound tryptophan in plasma. (1978). Trypto-phan loading: consequent effects on the synthesis of kynurenine and 5-hydroxyindoles in rat brain.