4-Bromohomoibotenic Acid Selectively Activates a 1-Aminocyclopentane-1S,3R-Dicarboxylic Acid-Insensitive Metabotropic Glutamate Receptor Coupled to Phosphoinositide Hydrolysis in Rat Cortical Slices
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 63, Issue 1, pages 133–139, July 1994
How to Cite
Chung, D. S., Winder, D. G. and Conn, P. J. (1994), 4-Bromohomoibotenic Acid Selectively Activates a 1-Aminocyclopentane-1S,3R-Dicarboxylic Acid-Insensitive Metabotropic Glutamate Receptor Coupled to Phosphoinositide Hydrolysis in Rat Cortical Slices. Journal of Neurochemistry, 63: 133–139. doi: 10.1046/j.1471-4159.1994.63010133.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received July 16, 1993; revised manuscript received October 14, 1993; accepted November 4, 1993.
- Bromohomoibotenic acid;
- 1-Aminocyclopentane-1S,3R-dicarboxylic acid;
- Metabotropic glutamate receptor;
- Phosphoinositide hydrolysis;
- Cyclic AMP
Abstract: Glutamate activates a family of receptors, known as metabotropic glutamate receptors (mGluRs), that are coupled to various second messenger systems through G proteins. All mGluR subtypes characterized to date in rat brain slices are activated by the glutamate analogue 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD). However, few agonists are available that selectively activate specific mGluR subtypes. We report that the glutamate analogue (R,S)-4-bromohomoibotenate (BrHI) stimulates phosphoinositide hydrolysis in rat cerebral cortical slices in a concentration-dependent manner (EC50 = 190 µM). The response to BrHI is stereoselective and is not blocked by ionotropic glutamate receptor antagonists. It is interesting that the responses to BrHI and 1S,3R-ACPD are completely additive, suggesting that these responses are mediated by different receptor subtypes. Consistent with this, the response to BrHI is insensitive to l-2-amino-3-phosphonopropionic acid (l-AP3), whereas the response to 1S,3R-ACPD is partially blocked by l-AP3. BrHI does not activate metabotropic receptors coupled to changes in cyclic AMP accumulation or activation of phospholipase D. Thus, BrHI seems to activate specifically a phosphoinositide hydrolysis-linked mGluR that is insensitive to 1S,3R-ACPD. This compound may prove useful as a tool for elucidating the roles of different mGluR subtypes in mammalian brain.