β-Adrenergic receptor modulation of the LPS-mediated depression in CYP1A activity in astrocytes

Dalya Abdulla, Kenneth W. Renton

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

18 Citas (Scopus)

Resumen

CYP1A1 and 1A2, two important P450 isoforms in the brain that metabolize many endogenous and exogenous substrates, are downregulated during central nervous system (CNS) inflammation. The stimulation of β-adrenergic receptors has been demonstrated to be anti-inflammatory in many cell types, leading us to hypothesize that stimulation of β-adrenergic receptors could prevent the downregulation in CYP1A1 and 1A2 activity in an in vitro model of CNS inflammation. Isoproterenol, a general β12 receptor agonist, and clenbuterol, a specific β2 receptor agonist, were both able to prevent the LPS-induced downregulation in CYP1A1/2 activity in astrocytes. The involvement of β-adrenergic receptors was confirmed using the general β12 receptor antagonist propranolol, which was able to abrogate the protection conferred by isoproterenol and clenbuterol in astrocytes treated with LPS. The isoproterenol and clenbuterol mediated protective effect on the LPS-induced downregulation in CYP1A activity was a cyclic AMP (cAMP) dependent process, since forskolin was able to mimic the protective effect. Isoproterenol and clenbuterol may also prevent the LPS-induced downregulation in CYP1A activity through changes in TNFα expression. Despite a slight reduction in the LPS-induced nuclear translocation of the p65 subunit of NF-κB, isoproterenol and clenbuterol had no effect on the DNA binding ability of this transcription factor, indicating that the β-adrenergic protective effects on CYP1A activity occurred independent of changes in NF-κB activity. The results presented in this paper reveal that β-adrenergic receptor stimulation can modulate cytochrome P450 activity in an in vitro model of CNS inflammation by a cAMP mediated pathway.

Idioma originalEnglish
Páginas (desde-hasta)741-750
Número de páginas10
PublicaciónBiochemical Pharmacology
Volumen69
N.º5
DOI
EstadoPublished - mar. 1 2005

Nota bibliográfica

Funding Information:
This work was supported by a grant from the Canadian Institute for Health Research (CIHR). Dalya Abdulla was funded by an Eliza Ritchie doctoral research award.

ASJC Scopus Subject Areas

  • Biochemistry
  • Pharmacology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Huella

Profundice en los temas de investigación de 'β-Adrenergic receptor modulation of the LPS-mediated depression in CYP1A activity in astrocytes'. En conjunto forman una huella única.

Citar esto