The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat

Administration of 2,4-diamino-6-hydroxypyrimidine (DAHP) in the diet of rats reduced total biopterins in plasma, brain and liver. The levels of dihydropteridine reductase (DHPR) and the rate of biopterin biosynthesis were unaffected. Animals on the DAHP diet consistently lost weight and ate less. He...

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Main Authors: Cox J., Armstrong R. A., Blair J. A.
Format: Article
Language:English
Published: De Gruyter 1991-09-01
Series:Pteridines
Online Access:https://doi.org/10.1515/pteridines.1991.3.3.185
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author Cox J.
Armstrong R. A.
Blair J. A.
author_facet Cox J.
Armstrong R. A.
Blair J. A.
author_sort Cox J.
collection DOAJ
description Administration of 2,4-diamino-6-hydroxypyrimidine (DAHP) in the diet of rats reduced total biopterins in plasma, brain and liver. The levels of dihydropteridine reductase (DHPR) and the rate of biopterin biosynthesis were unaffected. Animals on the DAHP diet consistently lost weight and ate less. Hence, the effects of DAHP and food restriction on biopterin metabolism, neurotransmitters and behaviour were investigated. Food restriction had similar effects to DAHP in that brain, liver and plasma biopterins were reduced. Neither DAHP nor food restriction significantly influenced the levels of neurotransmitters in the brain. However, DAHP reduced general activity and rearing of the animals in an open field arena while food restriction increased these parameters. These results suggest that the behavioural changes are either due to neurotransmitter changes not revealed by gross brain neurochemical analyses or to a more direct effect of tetrahydrobiopterin. In addition, the effects of DAHP may be confounded to some degree with these of reduced dietary intake and this has implications for the use of DAHP as an animal model of tetrahydrobiopterin (BH4) deficiency.
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spelling doaj.art-e534ae5ad180453fb951dd7a3350ae852022-12-21T21:49:28ZengDe GruyterPteridines0933-48072195-47201991-09-013318518910.1515/pteridines.1991.3.3.185The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the RatCox J.0Armstrong R. A.1Blair J. A.2Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.Department of Vision Sciences, Aston University, Aston Triangle, Birmingham B4 7 ET, U.K.Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.Administration of 2,4-diamino-6-hydroxypyrimidine (DAHP) in the diet of rats reduced total biopterins in plasma, brain and liver. The levels of dihydropteridine reductase (DHPR) and the rate of biopterin biosynthesis were unaffected. Animals on the DAHP diet consistently lost weight and ate less. Hence, the effects of DAHP and food restriction on biopterin metabolism, neurotransmitters and behaviour were investigated. Food restriction had similar effects to DAHP in that brain, liver and plasma biopterins were reduced. Neither DAHP nor food restriction significantly influenced the levels of neurotransmitters in the brain. However, DAHP reduced general activity and rearing of the animals in an open field arena while food restriction increased these parameters. These results suggest that the behavioural changes are either due to neurotransmitter changes not revealed by gross brain neurochemical analyses or to a more direct effect of tetrahydrobiopterin. In addition, the effects of DAHP may be confounded to some degree with these of reduced dietary intake and this has implications for the use of DAHP as an animal model of tetrahydrobiopterin (BH4) deficiency.https://doi.org/10.1515/pteridines.1991.3.3.185
spellingShingle Cox J.
Armstrong R. A.
Blair J. A.
The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
Pteridines
title The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
title_full The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
title_fullStr The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
title_full_unstemmed The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
title_short The Influence of 2,4-Diamino-6-Hydroxypyrimidine and Food Restriction on Tetrahydrobiopterin Metabolism, Neurotransmitters and Behaviour in the Rat
title_sort influence of 2 4 diamino 6 hydroxypyrimidine and food restriction on tetrahydrobiopterin metabolism neurotransmitters and behaviour in the rat
url https://doi.org/10.1515/pteridines.1991.3.3.185
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