Corticotropin-releasing factor receptor antagonist attenuates LPS-induced increase of GTP cyclohydrolase I expression at murine locus coeruleus

Yoko S. Kaneko, Keiji Mori, Akira Nakashima, Ikuko Nagatsu, Toshiharu Nagatsu, Akira Ota

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

It has been reported that corticotropin-releasing factor (CRF) is involved in the regulation of norepinephrine neuron responses to stress such as an immobilized stress. Furthermore, systemic lipopolysaccharide (LPS) injection upregulates the transcription of the genes encoding CRF and CRF type 1 receptor in the paraventricular nucleus of the hypothalamus. We have already reported that an increase in norepinephrine turnover within the murine locus coeruleus is accompanied by septic shock triggered by LPS intraperitoneal injection. We also elucidated that the expression levels of the enzymes involved in the catecholamine biosynthesis were altered by peripheral LPS injection. Collectively, the effects of CRF on the expression levels of the enzymes at murine locus coeruleus were investigated by peripherally injecting CP-154,526, a CRF receptor type 1 antagonist. Pretreatment with CP-154,526 attenuated the increase in expression levels of GTP cyclohydrolase I mRNA due to intraperitoneal LPS injection at 4 h after the injection. However, no effects on the expression level of tyrosine hydroxylase mRNA at the site were observed. Taken together with the fact that LPS injection enhances tetrahydrobiopterin biosynthesis at locus coeruleus, CP-154,526 may attenuate the increase of NE turnover by suppressing the enhanced GCH expression level at the site caused by peripheral LPS injection.

Original languageEnglish
Pages (from-to)289-297
Number of pages9
JournalBiogenic Amines
Volume19
Issue number4-6
DOIs
Publication statusPublished - 01-12-2005

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Pharmacology

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