A number of studies have implicated glutamate excitotoxcity in the neostriatal neuronal degeneration typical of Huntington's disease. It has also been noticed that both pre- and postsynaptic metabotropic glutamate receptors (mGluRs) may act to modify neuronal sensitivity to exitotoxic compounds in animal models of this disorder. Along these lines,, presynaptic Mglurs can be found on cortical projections into the stratum and are known to modulate glutamatergic transmission at these synapse, presumably via mechanisms which may involve calcium and/or potassium channels. Additionally, postsynaptic Mglurs are known to couple to phosphatydyl inositol metabolism and the mobilization of intracellular calcium in striatal neurons. Mglurs may therefore encourage either neuroprotective or neurodegenerative processes depending upon the signal transduction pathway to which they couple. To better understand the role of these receptors in the neostriatum and to assess their potential as targets for pharmacologic intervention in huntington's disease, the function of mGluR receptor subtypes will be assessed in both native and heterologous systems. This characterization may eventually allow for development of effective treatments for striatal degenerative disorders like Huntington's disease.
| McCool, B A; Lovinger, D M (1995) Ifenprodil inhibition of the 5-hydroxytryptamine3 receptor. Neuropharmacology 34:621-9 |
