SULFUR-CONTAINING AMINO-ACIDS ARE AGONISTS FOR GROUP-1 METABOTROPIC RECEPTORS EXPRESSED IN CLONAL RCT CELL-LINES

Comparison of the pharmacological effects of a range of sulphur-contai ning amino acids on human mGluR1 alpha and mGluR5a has been undertaken , cDNAs of each mGluR were transfected into a Syrian hamster tumour ce ll line AV12-664 that was previously transfected with the rat glutamat e-aspartate transporter protein (GLAST). The L-isomers of cysteine sul phinic acid (CSA), homocysteine sulphinic acid (HCSA), cysteic acid (C A) and serine-O-sulphate (SOS) stimulated PI hydrolysis in human mGluR 1 alpha and mGluR5a cells with full agonist effects. D-CSA, the only a ctive D-isomer, was a partial agonist for mGluR5a whereas L-sulphocyst eine (S-CYS) showed weak agonist-like effects at high concentrations o n both mGluR1 alpha and mGluR5a. L-Homocysteic acid was inactive on bo th mGluR1 alpha and mGluR5a cells. Treatment of mGluR cultures with gl utamate pyruvate transaminase did not alter the potencies of the S-ami no acids on PI hydrolysis responses. Inhibitor constants (K-i) obtaine d for L-HCSA, L-CSA, L-CA and L-SOS in [H-3]glutamate receptor binding studies with mGluR1 alpha cells indicated that L-HCSA, L-CSA, L-CA an d L-SOS can bind specifically to mGluR1 with L-HCSA showing the highes t affinity. These results confirm that certain endogenously produced S -amino acids may interact directly with group 1 mGluRs. (C) 1998 Elsev ier Science Ltd. All rights reserved.