Abstract
Metabotropic glutamate receptors (mGluRs) were initially discovered by their unique coupling mechanism and pharmacological characteristics. This was preceded by the recognition in the early 1980s of phosphoinositide hydrolysis as a novel signal transduction pathway in the mammalian central nervous system (CNS) (Berridge and Irvine, 1984; Nishizuka, 1984). Pharmacological studies of receptor-mediated phosphoinositide hydrolysis in CNS tissues were greatly facilitated by use of lithium ion to amplify agonist-dependent responses. Lithium at concentrations of 1–10 mM uncompetitively inhibits the enzyme inositol-1-monophosphatase (Hallcher and Sherman, 1980). Using 3H-myo-inositol to label 3H-phosphoinositides and lithium to inhibit inositol-l-monophosphatase, Berridge et al. (1982) demonstrated in rat cerebral cortical slices that cholinergic and adrenergic receptor agonists will increase phosphoinositide hydrolysis and, thus, produce an easily measured increase in the formation of 3H-inositol-1-monophosphate. The use of this sensitive technique allowed other investigators to begin characterizing the various receptor systems that were linked to this novel second-messenger system in the CNS (see Fisher and Agranoff, 1987).
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Schoepp, D.D. (1994). Pharmacological Properties of Metabotropic Glutamate Receptors. In: Conn, P.J., Patel, J. (eds) The Metabotropic Glutamate Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2298-7_2
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