BRAIN BIOPTERIN METABOLISM IN CHRONIC EXPERIMENTAL HEPATIC-ENCEPHALOPATHY

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome ass ociated with a substantial increase in the brain L-tryptophan (L-TRP) level. Moreover, a supranormal L-TRP hydroxylating activity in the bra in suggests an induced enzymatic process in chronic HE. GTP-cyclohydro lase I (GTPCHI) and tetrahydrobiopterin (BH4) are two major factors be sides L-TRP that are involved in regulating the brain L-TRP hydroxylat ing activity. We therefore determined the GTPCHI activity, the total b iopterin and the BH4 concentrations in the neocortex and mesencephalon -pons of portacaval shunted (PCS) rats. The encephalopathic component in PCS rats was accounted for by studying open field behaviour. The ac ute effects of a single parenteral L-TRP challenge were also evaluated . The basal GTPCHI activities in PCS rats were decreased bu 50% (p<0.0 5) compared to controls in both investigated brain regions. No signifi cant alterations in brain total biopterin or BH4 levels were present. The PCS rats exhibited a clearly reduced spontaneous locomotor activit y. After the exogenous L-TRP load only a lower GTPCHI activity in the neocortex of PCS rats was recorded. We conclude that a perturbation in the brain biopterin metabolism is concomitantly present with behaviou ral abnormalities in the chronic PCS condition and that the acute effe cts of a superimposed L-TRP load do not aggravate these disturbances.