Desensitization of group I metabotropic glutamate receptors in rat sympathetic neurons

Journal of Neurophysiology
Paul J Kammermeier, Stephen R Ikeda

Abstract

Desensitization of heterologously expressed metabotropic glutamate receptor 5a (mGluR5a) was examined in rat sympathetic neurons. Calcium currents in cells expressing mGluR5a exhibited substantial inhibition in response to glutamate exposure. In the continued presence of glutamate, inhibition attenuated rapidly over the course of about a minute. Desensitization was eliminated when a nonhydrolyzable ATP analogue was substituted for ATP in the pipette solution, suggesting that desensitization was mediated by a phosphorylation event. Next, pharmacological agents were used to investigate the nature of the kinase involved in desensitization. Desensitization was sensitive to the nonspecific kinase inhibitor, staurosporine, but not H-7, another nonspecific kinase inhibitor. Inhibitors of myosin light chain kinase and calmodulin-dependent kinase were without effect on desensitization. However, desensitization was sensitive to the protein kinase C inhibitor bisindolymaleimide. In contrast, Gö6976, a selective inhibitor of conventional protein kinase C isoforms, was without effect. In addition, desensitization persisted in the presence of 10 mM intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, a fast Ca(2+) chelator. Finally...Continue Reading

References

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Citations

Aug 1, 2007·Journal of Neuroscience Research·Chul Hoon KimKatherine W Roche
Jun 12, 2004·Journal of Biomolecular Screening·Elfrida R BenjaminKenneth J Valenzano
Nov 2, 2005·Nature Reviews. Neuroscience·David Attwell, Alasdair Gibb
Oct 19, 2014·Molecular Pharmacology·Yuh-Jiin I JongKaren L O'Malley
Mar 14, 2007·Trends in Pharmacological Sciences·Stephen S G Ferguson

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