Cloning and characterization of a bifunctional metabotropic receptor activated by both extracellular calcium and glutamate

A cDNA from salmon brain which induces a consistent activation of Ca2+ dependent Cl- (Ca2+-Cl-) current in Xenopus oocytes in the saline solution was isolated by an expression cloning method, The primary structure showed a high homology with the metabotropic glutamate receptors (mGluR), and a limited homology with the Ca2+/polyvalent cation receptors (CaR), The encoded protein was functionally characterized for the sensitivity to extracellular Ca2+ (Ca-0(2+)), and the consistent activation of Ca2+-Cl- current was determined to be due to Ca2+ contained in the saline solution, It was also confirmed that the encoded protein has a function to sense glutamate. An increase in inositol 1,4,5-triphosphate turnover was observed when either Ca2+ or glutamate was applied. Thus, the encoded protein was identified as a bifunctional metabotropic receptor for both Ca2+ and glutamate, In addition, rat mGluR1 alpha was also shown to be activated by Ca-0(2+). This is the first report of a G-protein coupled receptor which is activated by two totally different physiological agonists.