Publication Details (including relevant citation information):
Johnson, Bryan G., Wright, Rebecca A., Arnold, M. Brian, Wheeler, William J., Ornstein, Paul L., Schoepp, Darryle D. Neuropharmacology 1999 38 (10) 1519-1529
Abstract: Metabotropic glutamate (mGlu) receptors are a family of eight known subtypes termed mGlu1-8. Currently, few ligands are available to study the pharmacology of mGlu receptor subtypes. In functional assays, we previously described LY341495 as a highly potent and selective mGlu2 and mGlu3 receptor antagonist. In this study, radiolabeled (3H)-LY341495 was used to investigate the characteristics of receptor binding to membranes from cells expressing human mGlu receptor subtypes. Using membranes from cells expressing human mGlu2 and mGlu3 receptors, (3H)-LY341495 (1 nM) specific binding was > 90% of total binding. At an approximate KD concentration for (3H)-LY341495 binding to human mGlu2 and mGlu3 receptors (1 nM), no appreciable specific binding of (3H-)LY341495 was found in membranes of cells expressing human mGlu1a, mGlu5a, mGlu4a, mGlu6, or mGlu7a receptors. However, modest (apprx 20% of mGlu2/3) specific (3H)-LY341495 (1 nM) binding was observed in human mGlu8 expressingcells. (3H)-LY341495 bound to membranes expressing human mGlu2 and mGlu3 receptors in a reversible and saturable manner with relatively high affinities (Bmax 20.5 +- 5.4 and 32.0 +- 7.0 pmol/mg protein; and KD = 1.67 +- 0.20 and 0.75 +- 0.43 nM, respectively). The pharmacology of (3H)-LY341495 binding in mGlu2 and mGlu3 expressing cells was consistent with that previously described for LY341495 in functional assays. (3H)-LY341495 binding provides a useful way to further investigate regulation of receptor expression and pharmacological properties of mGlu2 and mGlu3 receptor subtypes in recombinant systems.