Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-21
pubmed:abstractText
GTP cyclohydrolase I is the first and rate-limiting enzyme for the de novo biosynthesis of tetrahydrobiopterin, which is the cofactor for tyrosine hydroxylase. Lipopolysaccharide can modulate tetrahydrobiopterin production by upregulating GTP cyclohydrolase I protein expression in the locus coeruleus in the mouse brain. The increased supply of tetrahydrobiopterin in the locus coeruleus leads to increased tyrosine hydroxylase activity without affecting the level of tyrosine hydroxylase protein expression, resulting in an increase in norepinephrine turnover at the site. This study was performed to address whether the increase in GTP cyclohydrolase I protein is dependent on the de novo synthesis of GCH in the locus coeruleus. After i.p. administration of lipopolysaccharide, the mRNA expression of GTP cyclohydrolase I was examined. The expression level increased within 2 h, and reached to maximum level at 4 h after the lipopolysaccharide administration. However, the mRNA expression level of 6-pyruvoyl-tetrahydropterin synthase and sepiapterin reductase, both of which are involved successively after GTP cyclohydrolase I in tetrahydrobiopterin biosynthesis, were not affected by the lipopolysaccharide administration. These results suggest that GTP cyclohydrolase I upregulation alone is enough to modulate tetrahydrobiopterin production in the locus coeruleus. In addition, the mRNA level of tyrosine hydroxylase was also not affected by the lipopolysaccharide administration. Taken together, the data indicate that GTP cyclohydrolase I plays a crucial role in regulating norepinephrine biosynthesis by a pathway the activity of which is triggered by lipopolysaccharide i.p. administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:copyrightInfo
Copyright 2003 IBRO
pubmed:issnType
Print
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Peripheral administration of lipopolysaccharide enhances the expression of guanosine triphosphate cyclohydrolase I mRNA in murine locus coeruleus.
pubmed:affiliation
Department of Physiology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't