Sulphur-containing amino acids are agonists for group 1 metabotropic receptors expressed in clonal RGT cell lines

Abstract

Comparison of the pharmacological effects of a range of sulphur-containing amino acids on human mGluR1 α and mGluR5a has been undertaken. cDNAs of each mGluR were transfected into a Syrian hamster tumour cell line AV12-664 that was previously transfected with the rat glutamate–aspartate transporter protein (GLAST). The l-isomers of cysteine sulphinic acid (CSA), homocysteine sulphinic acid (HCSA), cysteic acid (CA) and serine- O-sulphate (SOS) stimulated PI hydrolysis in human mGluR1 α and mGluR5a cells with full agonist effects. d-CSA, the only active d-isomer, was a partial agonist for mGluR5a whereas l-sulphocysteine ( S-CYS) showed weak agonist-like effects at high concentrations on both mGluR1 α and mGluR5a. l-Homocysteic acid was inactive on both mGluR1 α and mGluR5a cells. Treatment of mGluR cultures with glutamate pyruvate transaminase did not alter the potencies of the S-amino acids on PI hydrolysis responses. Inhibitor constants ( K i) obtained for l-HCSA, l-CSA, l-CA and l-SOS in [ 3H]glutamate receptor binding studies with mGluR1 α cells indicated that l-HCSA, l-CSA, l-CA and l-SOS can bind specifically to mGluR1 with l-HCSA showing the highest affinity. These results confirm that certain endogenously produced S-amino acids may interact directly with group 1 mGluRs.