title: Baclofen influences lipopolysaccharide-mediated interleukin-6 release from murine pituicytes.
abstract: Pituicytes, the glial cells of the neurohypophysis, secrete interleukin-6 upon stimulation with various inflammatory mediators, i.e. lipopolysaccharide. Previous studies have identified several receptors on pituicytes. This study investigates the effect of GABA(B) receptor activation on interleukin-6 release from pituicytes. Cultured murine pituicytes were stimulated for 24 h with lipopolysaccharide (0.5 ng/ml) to give a significant interleukin-6 release compared to control. The interleukin-6 release was significantly potentiated by the GABA(B) receptor agonist (R)-4-amino-3-(4-chlorophenyl) butanoic acid (R-baclofen; 10, 100 or 500 microM). However, R-baclofen itself (10, 100 or 500 microM) did not stimulate the interleukin-6 secretion. Furthermore, the potent GABA(B) receptor antagonists 3-[[(3,4-Dichlorophenyl)methyl]amino]propyl]diethoxymethyl) phosphinic acid (CGP52432; 30 or 300 microM) and (RS)-3-Amino-2-(4-chlorophenyl)-2-hydroxypropyl-sulphonic acid (2-OH-saclofen; 10 or 100 microM) did not remove the effect of R-baclofen (100 microM). Gamma-amino butyric acid (GABA; 30 or 300 microM) did not alter the lipopolysaccharide-mediated interleukin-6 response. After 30 min, intracellular cyclic AMP (cAMP) was higher in cells stimulated with lipopolysaccharide compared to control, and R-baclofen significantly inhibited this increase in cAMP. Nevertheless, neither lipopolysaccharide nor R-baclofen had any effect on intracellular cAMP after 24 h of stimulation. The results suggest that the effect of R-baclofen on lipopolysaccharide-stimulated interleukin-6 secretion is independent of GABA(B) receptors.
authors.affiliation: Department of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark. tikl@dfh.dk
authors.forename: Tine H
authors.initials: TH
authors.lastname: Kjeldsen
authors.forename: Erik W
authors.initials: EW
authors.lastname: Hansen
authors.forename: Jens D
authors.initials: JD
authors.lastname: Christensen
authors.forename: Lise
authors.initials: L
authors.lastname: Moesby
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002478:Cells, Cultured; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D001418:Baclofen