Adrenocorticotropin, vasoactive intestinal polypeptide, growth hormone-releasing factor, and dynorphin compete for common receptors in brain and adrenal.
Adrenocorticotropin, vasoactive intestinal polypeptide, growth hormone-releasing factor, and dynorphin compete for common receptors in brain and adrenal.
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促肾上腺皮质激素、血管活性肠多肽、生长激素释放因子和强啡肽竞争大脑和肾上腺中的常见受体。
DOI：
10.1210/endo-126-3-1327
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发表时间：
1990
期刊：
影响因子：
4.8
通讯作者：
F. LaBella
中科院分区：
文献类型：
--
作者：
Z. G. Li;G. Queen;F. LaBella
本实验室之前的研究表明，血管活性肠多肽（VIP）、gh释放因子（GRF）和肌啡肽（DYN）可以抑制[125I]ACTH-(1-24)与大鼠脑膜的高亲和力结合，但其他肽则不受影响。我们现在发现这些肽在脑内竞争[125I]VIP结合和在肾上腺皮质竞争[125I]ACTH-(1-24)结合，并促进类固醇生成。[125I]ACTH-(1-24)在大鼠脑和牛肾上腺的高亲和力位点Kd值分别为0.51 +/- 0.41和3.9 +/- 1.3 nM；VIP的Ki值分别为5.4 +/- 4.2 nM和1.4 +/- 0.51 nM。在大鼠脑和牛肾上腺中，[125I]VIP的高亲和力位点Kd值分别为2.9 +/- 1.7和0.5 +/- 0.8 nM， ACTH的Ki值分别为23.6 +/- 14.0和22.2 +/- 33.0 nM。在脑内，DYN和GRF分别在Ki值为49和30 nM时抑制[125I]VIP的结合。10(-10) M ACTH、VIP、DYN或GRF显著刺激了分离的牛肾上腺皮质细胞的皮质醇分泌，每种细胞的最大反应发生在10(-8)M。然而，VIP、DYN或GRF的最大皮质醇分泌量仅为ACTH-的一半左右（1-24）。ACTH-(1-24)和VIP （10(-10) M）的联合作用在刺激皮质醇产生方面是加性的，而10(-8)M的联合作用并不比单独使用ACTH产生更大的反应。VIP加ACTH-有加性类固醇效应（1-10），而VIP加ACTH-无加性类固醇效应（11-24）。未标记的ACTH-(11-24)、ACTH-(1-24)、VIP、GRF和DYN可抑制[125I]ACTH-(11-24)在肾上腺膜上的特异性结合，但ACTH-(1-10)、肽T、TRH、α - MSH或β -内啡肽不能抑制[125I]ACTH-(11-24)；[125I]ACTH-无特异性结合（1-10）。功能研究和结合数据，结合同源氨基酸序列的存在，表明VIP、GRF和DYN在ACTH受体亚群中相互作用，识别ACTH分子11-24序列内的片段。
It was previously shown in this laboratory that high affinity binding of [125I]ACTH-(1-24) to membranes from rat brain was inhibited by vasoactive intestinal polypeptide (VIP), GH-releasing factor (GRF), and dynorphin (DYN), but not by other peptides tested. We now show that these peptides compete for [125I]VIP binding in brain and for [125I]ACTH-(1-24) binding in adrenal cortex and promote steroidogenesis. The high affinity sites for [125I]ACTH-(1-24) in the rat brain and bovine adrenal had Kd values of 0.51 +/- 0.41 and 3.9 +/- 1.3 nM, respectively; and the Ki values for VIP were 5.4 +/- 4.2 and 1.4 +/- 0.51 nM, respectively. In rat brain and bovine adrenal the high affinity site for [125I]VIP had Kd values of 2.9 +/- 1.7 and 0.5 +/- 0.8 nM, respectively, and Ki values for ACTH of 23.6 +/- 14.0 and 22.2 +/- 33.0 nM, respectively. In brain, DYN and GRF inhibited binding of [125I]VIP with Ki values of 49 and 30 nM, respectively. Cortisol secretion from isolated bovine adrenal cortical cells was significantly stimulated by 10(-10) M ACTH, VIP, DYN, or GRF, and a maximal response occurred for each at 10(-8) M. However, maximal cortisol production in response to VIP, DYN, or GRF was only about half that by ACTH-(1-24). The combination of ACTH-(1-24) and VIP, each at 10(-10) M, was additive in stimulating cortisol production, whereas each at 10(-8) M caused no greater response than ACTH alone. There was an additive steroidogenic effect of VIP plus ACTH-(1-10), but not VIP plus ACTH-(11-24). Specific binding of [125I]ACTH-(11-24) in adrenal membranes was inhibited by unlabeled ACTH-(11-24), ACTH-(1-24), VIP, GRF, and DYN, but not by ACTH-(1-10), peptide T, TRH, alpha MSH, or beta-endorphin; there was no specific binding of [125I]ACTH-(1-10). Functional studies and binding data, in conjunction with the existence of homologous amino acid sequences, indicate that VIP, GRF, and DYN interact at a subpopulation of ACTH receptors that recognizes a moiety within the 11-24 sequence of the ACTH molecule.
合成促肾上腺皮质激素类似物，在碘化后保留完整的生物活性。
影响因子：
4.8
作者：
Buckley,DI;Yamashiro,D;Ramachandran,J
通讯作者：
Ramachandran,J
促肾上腺皮质激素受体的放射性探针。
影响因子：
2.9
作者：
Hofmann,K;Romovacek,H;Stehle,CJ;Finn,FM;Bothner-By,AA;Mishra,PK
通讯作者：
Mishra,PK
血管活性肠肽刺激肾上腺醛固酮和皮质酮的分泌。
影响因子：
4.8
作者：
Cunningham,LA;Holzwarth,MA
通讯作者：
Holzwarth,MA