Deshpande S B, Warnick J E
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Eur J Pharmacol. 1994 Dec 27;271(2-3):439-44. doi: 10.1016/0014-2999(94)90804-4.
The efficacy of thyrotropin-releasing hormone (TRH) and its analogs to potentiate the spinal monosynaptic reflex was studied in isolated cords. The analogs examined were L-pyro-2-aminoadipyl-histidyl-thizolidine-4-carboxyamide (MK-771); pyroglutamyl-histidyl-prolineamide (TRH); pyroglutamyl-L-histidyl-3,3'-dimethyl-prolineamide (RX77368); (3-methyl-His2)TRH(methyl-TRH); gamma-buturolactone-gamma-carbonyl-histidyl-prolineamide citrate (DN-1417); pyroglutamyl-histidyl-proline (TRH-free acid); and histidyl-proline-diketopiperazine (cyclo(His-Pro)). The TRH analogs potentiated the monosynaptic reflex in a dose-dependent manner and the maximal potentiation occurred at about 1 microM. TRH-free acid potentiated the monosynaptic reflex but the maximal potentiation occurred at 100 times the TRH concentration. Cyclo(His-Pro) was totally ineffective. The concentration required to potentiate the monosynaptic reflex by 50% of the maximal response (EC50) was taken as an index for comparing various analogs in relation to TRH. The EC50 values of the analogs did not differ significantly from each other. However, the ratio of the mean value of an analog to that of TRH was of the following order: MK-771 (N- and C-terminally altered) > or = TRH > or = DN-1417 (N-terminal) > or = methyl-TRH > or = RX77368 (C-terminal) >>> TRH-free acid. Cyclo(His-Pro) was ineffective.
在离体脊髓中研究了促甲状腺激素释放激素（TRH）及其类似物增强脊髓单突触反射的功效。所检测的类似物有L-焦谷-2-氨基己二酰-组氨酰-噻唑烷-4-甲酰胺（MK-771）；焦谷氨酰-组氨酰-脯氨酰胺（TRH）；焦谷氨酰-L-组氨酰-3,3'-二甲基-脯氨酰胺（RX77368）；（3-甲基-组氨酸2）TRH（甲基-TRH）；γ-丁内酯-γ-羰基-组氨酰-脯氨酰胺柠檬酸盐（DN-1417）；焦谷氨酰-组氨酰-脯氨酸（TRH游离酸）；以及组氨酰-脯氨酸二酮哌嗪（环（组氨酸-脯氨酸））。TRH类似物以剂量依赖方式增强单突触反射，最大增强作用出现在约1微摩尔处。TRH游离酸增强单突触反射，但最大增强作用出现在TRH浓度的100倍时。环（组氨酸-脯氨酸）完全无效。将使单突触反射增强至最大反应的50%所需的浓度（EC50）作为比较各种类似物与TRH相关情况的指标。各类似物的EC50值彼此无显著差异。然而，一种类似物的平均值与TRH平均值的比值顺序如下：MK-771（N端和C端改变）≥TRH≥DN-1417（N端）≥甲基-TRH≥RX77368（C端）＞＞＞TRH游离酸。环（组氨酸-脯氨酸）无效。
