Sharif N A, Burt D R
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21021.
Neurosci Lett. 1987 Oct 29;81(3):339-44. doi: 10.1016/0304-3940(87)90407-1.
Guanine nucleotides inhibited the specific binding of 3Hthyrotropin-releasing hormone ([3H]MeTRH) to receptors for TRH in washed homogenates of rat anterior pituitary gland in a dose-related manner. The order of potency (at 100 and 500 microM final) was Gpp(NH)p (a stable analog of GTP) greater than GTP much greater than GDP much greater than cGMP (with the adenine nucleotides being inactive) in the pituitary and various brain regions. Gpp(NH)p at 1 mM caused 17-35% inhibition of [3H]MeTRH binding to different tissues including the pituitary, hypothalamus, retina and nucleus accumbens. A statistically significant nucleotide effect was not observed, however, in the olfactory bulb and medulla/pons membranes. Gpp(NH)p (1 mM) increased the dissociation constants for [3H]MeTRH binding by 1.9- to 2.4-fold in the pituitary, n. accumbens and retinal preparations without altering the apparent binding capacity. These data suggest that TRH receptor binding can be allosterically regulated by guanine nucleotides and provide further evidence for the existence of guanine nucleotide binding protein(s) coupled to the TRH receptor.
鸟嘌呤核苷酸以剂量相关的方式抑制3H促甲状腺激素释放激素([3H]MeTRH)与大鼠垂体前叶匀浆洗涤物中促甲状腺激素释放激素(TRH)受体的特异性结合。在垂体和不同脑区，效力顺序(终浓度为100和500 microM时)为：Gpp(NH)p(一种GTP的稳定类似物)＞GTP＞＞GDP＞＞cGMP(腺嘌呤核苷酸无活性)。1 mM的Gpp(NH)p对[3H]MeTRH与包括垂体、下丘脑、视网膜和伏隔核在内的不同组织的结合产生17% - 35%的抑制。然而，在嗅球和延髓/脑桥膜中未观察到统计学上显著的核苷酸效应。1 mM的Gpp(NH)p使[3H]MeTRH在垂体、伏隔核和视网膜制剂中的结合解离常数增加1.9至2.4倍，而不改变表观结合容量。这些数据表明，TRH受体结合可被鸟嘌呤核苷酸变构调节，并为与TRH受体偶联的鸟嘌呤核苷酸结合蛋白的存在提供了进一步证据。
