alpha(1)-Adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes.

Astrocytic responses to activation of metabotropic glutamate receptors grou p I (mGluRs I) and alpha (1)-adrenoreceptors in cultured cells have been as sessed using spectral analyzes and calcium imaging. Concentration-dependent changes were observed after stimulation with the mGluR I agonist (S)-3,5-d ihydroxyphenylglycine (DHPG). These responses changed from a regular low fr equency signal with sharp peaks at 1 muM to a pronounced stage of irregular ity at 10 muM. After stimulation with 100 muM the signal was again homogeno us in shape and regularity but occurred at a higher frequency. In contrast, the spectral properties after stimulation with the alpha (1)-adrenorecepto r agonist phenylephrine, exhibited considerable variation for all investiga ted concentrations. DHPG-induced increases in [Ca2+](i) were also associate d with astroglial glutamate release, whereas no release was observed after noradrenergic stimulation. Both DHPG-mediated calcium signaling and glutama te release were inhibited by preincubation with 10 or 100 muM phenylephrine . Collectively, the present investigation provides new information about th e spatial-temporal characteristics of astroglial intracellular calcium resp onses and demonstrates distinct differences between noradrenergic and gluta matergic receptors regarding intracellular calcium signaling and coupling t o 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.