Exciting Times beyond the Brain: Metabotropic Glutamate Receptors in Peripheral and Non-Neural Tissues

Metabotropic glutamate (mGlu) receptors are G-protein-coupled receptors expressed primarily on neurons and glial cells, where they are located in the proximity of the synaptic cleft. In the central nervous system (CNS), mGlu receptors modulate the effects of L-glutamate neurotransmission in addition to that of a variety of other neurotransmitters. However, mGlu receptors also have a widespread distribution outside the CNS that has been somewhat neglected to date. Based on this expression, diverse roles of mGlu receptors have been suggested in a variety of processes in health and disease including controlling hormone production in the adrenal gland and pancreas, regulating mineralization in the developing cartilage, modulating lymphocyte cytokine production, directing the state of differentiation in embryonic stem cells, and modulating gastrointestinal secretory function. Understanding the role of mGlu receptors in the periphery will also provide a better insight into potential side effects of drugs currently being developed for neurological and psychiatric conditions. This review summarizes the new potential roles of mGlu receptors and raises the possibility of novel pharmacological targets for various disorders.