Sulphur-containing amino acids are agonists for group 1 metabotropic receptors expressed in clonal RGT cell lines.
Comparison of the pharmacological effects of a range of sulphur-containing amino acids on human mGluR1alpha 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 mGluR1alpha 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 mGluR1alpha and mGluR5a. L-Homocysteic acid was inactive on both mGluR1alpha 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 (Ki) obtained for L-HCSA, L-CSA, L-CA and L-SOS in [3H]glutamate receptor binding studies with mGluR1alpha 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.
Lilly Research Centre, Eli Lilly, Windlesham, Surrey, UK.
A E
AE
Kingston
J
J
Lowndes
N
N
Evans
B
B
Clark
R
R
Tomlinson
J P
JP
Burnett
N G
NG
Mayne
S L
SL
Cockerham
D
D
Lodge
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003544:Cysteic Acid / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008647:Mesocricetus; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives / Q000494:pharmacology
D000603:Amino Acids, Sulfur; C578935:GRM5 protein, human; D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D006710:Homocysteine; C010982:homocysteinesulfinic acid; D018698:Glutamic Acid; D012694:Serine; C036040:serine O-sulfate; D003544:Cysteic Acid; D003545:Cysteine; C013461:cysteine sulfinic acid