title: Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes.
abstract: Astrocytic responses to activation of metabotropic glutamate receptors group I (mGluRs I) and alpha(1)-adrenoreceptors in cultured cells have been assessed using spectral analyzes and calcium imaging. Concentration-dependent changes were observed after stimulation with the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG). These responses changed from a regular low frequency signal with sharp peaks at 1 microm to a pronounced stage of irregularity at 10 microm. After stimulation with 100 microm the signal was again homogenous in shape and regularity but occurred at a higher frequency. In contrast, the spectral properties after stimulation with the alpha(1)-adrenoreceptor agonist phenylephrine, exhibited considerable variation for all investigated concentrations. DHPG-induced increases in [Ca(2+)](i) were also associated with astroglial glutamate release, whereas no release was observed after noradrenergic stimulation. Both DHPG-mediated calcium signaling and glutamate release were inhibited by preincubation with 10 or 100 microm phenylephrine. Collectively, the present investigation provides new information about the spatial-temporal characteristics of astroglial intracellular calcium responses and demonstrates distinct differences between noradrenergic and glutamatergic receptors regarding intracellular calcium signaling and coupling to glutamate release. The noradrenergic modulation of DHPG-induced responses indicates that intracellular astroglial processes can be regulated in a bi-directional feedback loop between closely connected astrocytes and neurons in the central nervous system.
authors.affiliation: Institute of Clinical Neuroscience, Göteborg University, Göteborg SE-413 45, Sweden. hakan.muyderman@anatcell.gu.se
authors.forename: H
authors.initials: H
authors.lastname: Muyderman
authors.forename: M
authors.initials: M
authors.lastname: Angehagen
authors.forename: M
authors.initials: M
authors.lastname: Sandberg
authors.forename: U
authors.initials: U
authors.lastname: Björklund
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: E
authors.initials: E
authors.lastname: Hansson
authors.forename: M
authors.initials: M
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D012118:Resorcinols / Q000737:chemistry
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D002118:Calcium; D005998:Glycine