Kingston A E, Lowndes J, Evans N, Clark B, Tomlinson R, Burnett J P, Mayne N G, Cockerham S L, Lodge D
Lilly Research Centre, Eli Lilly, Windlesham, Surrey, UK.
Neuropharmacology. 1998;37(3):277-87. doi: 10.1016/s0028-3908(98)00018-5.
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.
已对一系列含硫氨基酸对人代谢型谷氨酸受体1α（mGluR1α）和代谢型谷氨酸受体5a（mGluR5a）的药理作用进行了比较。将每种mGluR的cDNA转染到叙利亚仓鼠肿瘤细胞系AV12 - 664中，该细胞系先前已转染大鼠谷氨酸 - 天冬氨酸转运蛋白（GLAST）。半胱氨酸亚磺酸（CSA）、高半胱氨酸亚磺酸（HCSA）、半胱氨酸（CA）和丝氨酸 - O - 硫酸盐（SOS）的L - 异构体在人mGluR1α和mGluR5a细胞中刺激磷脂酰肌醇（PI）水解，具有完全激动剂作用。唯一具有活性的D - 异构体D - CSA是mGluR5a的部分激动剂，而L - 磺基半胱氨酸（S - CYS）在高浓度时对mGluR1α和mGluR5a均表现出弱激动剂样作用。L - 高半胱氨酸对mGluR1α和mGluR5a细胞均无活性。用谷氨酸丙酮酸转氨酶处理mGluR培养物不会改变S - 氨基酸对PI水解反应的效力。在对mGluR1α细胞进行的[³H]谷氨酸受体结合研究中，L - HCSA、L - CSA、L - CA和L - SOS的抑制常数（Ki）表明，L - HCSA、L - CSA、L - CA和L - SOS可特异性结合mGluR1，其中L - HCSA表现出最高亲和力。这些结果证实某些内源性产生的S - 氨基酸可能直接与1组mGluRs相互作用。
