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Metabolic Brain Disease

, Volume 10, Issue 2, pp 143–157 | Cite as

Brain biopterin metabolism in chronic experimental hepatic encephalopathy

  • Peter B. F. Bergqvist
  • Ernst R. Werner
  • Gustav Apelqvist
  • Mogens Bugge
  • Helmut Wachter
  • Finn Bengtsson
Article

Abstract

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with a substantial increase in the brain L-tryptophan (L-TRP) level. Moreover, a supranormal L-TRP hydroxylating activity in the brain suggests an induced enzymatic process in chronic HE. GTP-cyclohydrolase I (GTPCHI) and tetrahydrobiopterin (BH4) are two major factors besides L-TRP that are involved in regulating the brain L-TRP hydroxylating activity. We therefore determined the GTPCHI activity, the total biopterin 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 acute effects of a single parenteral L-TRP challenge were also evaluated. The basal GTPCHI activities in PCS rats were decreased bu 50% (p<0.05) compared to controls in both investigated brain regions. No significant alterations in brain total biopterin or BH4 levels were present. The PCS rats exhibited a clearly reduced spontaneous locomotor activity. 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 behavioural abnormalities in the chronic PCS condition and that the acute effects of a superimposed L-TRP load do not aggravate these disturbances.

Key words

Exploratory behaviour GTP-cyclohydrolase I L-tryptophan portacaval shunt portal-systemic encephalopathy spontaneous locomotor activity tetrahydrobiopterin 

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Peter B. F. Bergqvist
    • 1
  • Ernst R. Werner
    • 3
  • Gustav Apelqvist
    • 1
  • Mogens Bugge
    • 2
  • Helmut Wachter
    • 3
  • Finn Bengtsson
    • 1
  1. 1.Department of Clinical PharmacologyLund University HospitalLundSweden
  2. 2.Department of Thoracic SurgeryUniversity of GothenburgGothenburgSweden
  3. 3.Institute for Medical Chemistry and BiochemistryUniversity of InnsbruckInnsbruckAustria

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