通过高效液相色谱法研究脑肽酶对促甲状腺激素释放激素（TRH）和（3-甲基组氨酸）TRH的失活作用。

Inactivation of thyrotropin-releasing hormone (TRH) and (3Me-His) TRH by brain peptidases studied by high-performance liquid chromatography.

作者信息

Griffiths E C, McDermott J R, Smith A I

出版信息

Neurosci Lett. 1982 Jan 22;28(1):61-5. doi: 10.1016/0304-3940(82)90209-9.

Abstract

High-performance liquid chromatography (HPLC) has been used to separate and identify the metabolites formed from thyrotrophin-releasing-hormone (TRH) and its hyperactive analogue, (3Me-His)TRH, by subcellular fractions from rat cortex, hypothalamus and thalamus. Deamidation by the proline endopeptidase and formation of histidylproline diketopiperazines by the pyroglutamyl aminopeptidase were found to be the major mechanisms of brain inactivation of both peptides; (3Me-His)TRH was slightly more stable than TRH in the presence of the brain peptidases, and with enhanced receptor binding affinity, this could explain its increased biological activity. The HPLC system used may be applicable to determining the mechanisms of brain inactivation of other TRH analogues and could also be used to define the pathways for inactivation of larger neuropeptides as well.

摘要

高效液相色谱法（HPLC）已被用于分离和鉴定由促甲状腺激素释放激素（TRH）及其活性增强类似物（3-甲基组氨酸）TRH在大鼠皮层、下丘脑和丘脑的亚细胞组分中形成的代谢产物。脯氨酸内肽酶催化的脱酰胺作用以及焦谷氨酰氨基肽酶催化形成组氨酰脯氨酸二酮哌嗪被发现是这两种肽在脑内失活的主要机制；在脑肽酶存在的情况下，（3-甲基组氨酸）TRH比TRH略稳定，并且由于其受体结合亲和力增强，这可以解释其生物活性的增加。所使用的HPLC系统可能适用于确定其他TRH类似物在脑内失活的机制，也可用于确定更大的神经肽的失活途径。