MAF was in receipt of a BBSRC Quota Studentship.
Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells†
Article first published online: 29 MAR 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 204, Issue 2, pages 704–713, August 2005
How to Cite
Foreman, M. A., Gu, Y., Howl, J. D., Jones, S. and Publicover, S. J. (2005), Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells. J. Cell. Physiol., 204: 704–713. doi: 10.1002/jcp.20353
- Issue published online: 26 MAY 2005
- Article first published online: 29 MAR 2005
- Manuscript Accepted: 13 DEC 2004
- Manuscript Received: 19 OCT 2004
- BBSRC studentship
Nitric oxide (NO) is pivotal to bone physiology. In the central nervous system constitutive, Ca2+-calmodulin regulated NO synthase activity and glutamate signalling are intimately linked. Since L-glutamate signalling occurs in bone and is implicated in bone regulation, we have investigated the effect of L-glutamate on NO synthase in bone-derived cells. Treatment of marrow stromal cells with L-glutamate reduced basal NO synthase activity by 40%. Imaging showed that L-glutamate caused a rapid, usually localised and slowly-reversible fall in [Ca2+]i. This effect was resistant to disruption of intracellular Ca2+ stores but sensitive to extracellular La3+ or omission of extracellular Ca2+, demonstrating that glutamate acts by inhibition of membrane Ca2+ influx. The only previous description of such an effect of L-glutamate is via activation of the group III receptor, mGluR6, in the retina. Using Western blotting and RT-PCR we detected mGluR6 protein and transcripts in marrow stromal cells. The effects of L-glutamate on NOS activity and [Ca2+]i in marrow stromal cells were abolished by a group III mGluR inhibitor, (S)-2-amino-2-methyl-4-phosphonobutyric acid. Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L-glutamate induced membrane hyperpolarisation (−16 ± 2 mV), which was also sensitive to group III mGluR inhibition. L-glutamate had no effect on cAMP levels. We conclude that activation of a group III mGluR in bone marrow stromal cells inhibits a Ca2+-permeable plasma membrane channel, reducing [Ca2+]i and suppressing generation of NO. These observations directly link bone L-glutamate signalling to processes central to bone growth and regulation. © 2005 Wiley-Liss, Inc.