Brain biopterin metabolism in chronic experimental hepatic encephalopathy.
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.
Bergqvist
P B
PB
Department of Clinical Pharmacology, Lund University, Sweden.
Werner
E R
ER
Apelqvist
G
G
Bugge
M
M
Wachter
H
H
Bengtsson
F
F
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D002908:Chronic Disease; D005106:Exploratory Behavior / Q000502:physiology; D006136:GTP Cyclohydrolase / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology
D001708:Biopterins; D012701:Serotonin; D014364:Tryptophan; D006136:GTP Cyclohydrolase; C003402:sapropterin