Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain.
Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain.
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DOI：
10.1016/0014-2999(89)90233-1
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发表时间：
1989-05
影响因子：
5
通讯作者：
S. Vonhof;I. Paakkari;G. Feuerstein;L. Cohen;V. Labroo
中科院分区：
文献类型：
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作者：
S. Vonhof;I. Paakkari;G. Feuerstein;L. Cohen;V. Labroo
[4(5)-氟-咪唑-His2]-TRH (4(5)-F-TRH)、[2-三氟甲基-咪唑-His2]-TRH (2-CF3-TRH)和[4(5)-三氟甲基-咪唑-His2]-TRH (4(5)-CF3-TRH)这三种新型TRH类似物的结合特性已在大鼠垂体中进行了评估。下丘脑、脑干和皮质组织。 4(5)-F-TRH 先前显示可引起类似于 TRH 的动脉升压反应和催乳素释放，以低微摩尔亲和力 (Ki= 7.5−13.5μM) 与 TRH 受体结合。2-CF3-TRH 是心血管活性较低但催乳素释放活性增加的类似物，显示 Ki 值为 3.3–4.9 μM。 4(5)-CF3-TRH 的生物活性与 2-CF3-TRH 相当，其结合亲和力实际上是非特异性的 (Ki= 0.39−1.01 mM)。因此得出结论，这些类似物的生物效应是通过[3H][3Me-His2]-TRH不识别的低亲和力TRH结合位点介导的，或者是通过不涉及TRH受体本身的机制介导的。
Binding properties of [4(5)-fluoro-imidazole-His2]-TRH (4(5)-F-TRH), [2-trifluoromethyl-imidazole-His2]-TRH (2-CF3-TRH) and [4(5)-trifluoromethyl-imidazole-His2]-TRH (4(5)-CF3-TRH), three novel TRH analogs, have been evaluated in rat pituitary, hypothalamus, brainstem and cortex tissue. 4(5)-F-TRH, previously shown to elicit arterial pressor responses and prolactin release similar to those of TRH, binds to TRH receptors with low, micromolar affinity (Ki= 7.5−13.5μM) 2-CF3-TRH, an analog of less cardiovascular but increased prolactin-releasing activity, shows Kivalues of 3.3–4.9 μM. 4(5)-CF3-TRH, which shows comparable biological activity to 2-CF3-TRH, demonstrates a binding affinity which is virtually nonspecific (Ki= 0.39−1.01 mM). It is therefore concluded that the biological effects of these analogs are mediated either through low affinity TRH binding sites not recognized by [3H][3Me-His2]-TRH or through mechanisms not involving TRH receptors as such.