| Popis: |
The group II metabotropic glutamate (mGlu2 and mGlu3) receptors are among the minority of glutamate receptors that primarily inhibit synaptic transmission by coupling to Gio, inhibiting adenylate cyclase and potassium channels. Our understanding of their physiologic role has advanced considerably with the discovery of systemically active and selective agonists, antagonists, and, most recently, subtype-selective allosteric modulators. The mGlu2/3 agonists, such as LY354740 (and its prodrug LY544344), show activity in a number of preclinical models of anxiety, psychosis, and drug abuse and as neuroprotectants. The anxiolytic actions of group II agents have subsequently been confirmed in humans, and represent an exciting breakthrough in the glutamate field. Emerging preclinical results with mGlu2/3 antagonists and potentiators of the mGlu2 receptor indicate that, despite a presynaptic localization distal to the synaptic active zone, significant glutamatergic tone can occur under some physiologic conditions. This chapter describes some mGlu2/3-selective pharmacologic tools, briefly discusses the different synaptic and glial localizations, and notes how these unique receptors may regulate synaptic transmission. |
