The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation.
The metabotropic glutamate receptor mGluR5, but not the closely related mGluR1, is expressed in cultured astrocytes, and this expression is up-regulated by specific growth factors. We investigated the capability and underlying mechanisms of mGluR5 to induce oscillatory responses of intracellular calcium concentration ([Ca2+]i) in cultured rat astrocytes. Single-cell [Ca2+]i recordings indicated that an mGluR-selective agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), elicits [Ca2+]i oscillations in good agreement with the growth factor-induced up-regulation of mGluR5 in cultured astrocytes. A protein kinase C (PKC) inhibitor, bisindolylmaleimide I, converted a 1S,3R-ACPD-mediated oscillatory response into a nonoscillatory response. In addition, the PKC activator phorbol 12-myristate 13-acetate completely abolished the [Ca2+]i increase. These and other pharmacological properties of 1S,3R-ACPD-induced [Ca2+]i oscillations correlate well with those of the cloned mGluR5 characterized in heterologous expression systems. Furthermore, the potential involvement of protein phosphatases in [Ca2+]i oscillations is suggested. The present study demonstrates that mGluR5 is capable of inducing [Ca2+]i oscillations in cultured astrocytes and that phosphorylation/dephosphorylation of mGluR5 is critical in [Ca2+]i oscillations, analogous to the cloned mGluR5 expressed in heterologous cell lines.
Nakahara
K
K
Department of Biological Sciences, Kyoto University Faculty of Medicine, Japan.
Okada
M
M
Nakanishi
S
S
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D015854:Up-Regulation
D006133:Growth Substances; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D011493:Protein Kinase C; D002118:Calcium