Pituitary somatostatin receptors. Characterization by binding with a nondegradable peptide analogue.
Pituitary somatostatin receptors. Characterization by binding with a nondegradable peptide analogue.
复制标题
垂体生长抑素受体。
DOI：
10.1016/s0021-9258(19)68162-7
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
D. Parker
中科院分区：
文献类型：
--
作者：
G. Aguilera;D. Parker
大鼠垂体中的生长抑素受体与放射性碘化的高亲和力生长抑素类似物125I-Tyr1[D-Trp8]生长抑素结合分析。该衍生物的受体结合在30分钟达到平衡，并保持至少60分钟的平台。两种L-Trp8标记的生长抑素类似物。125I-Tyr1-和[125I-Tyr11]生长抑素表现出较不稳定和较低的特异性摄取和较高的非特异性结合。与L-Trp8配体在结合实验中快速降解相反，125I-Tyr1]D-Trp8]生长抑素在与垂体颗粒孵育90分钟后保留了80%以上的结合活性。垂体颗粒结合125I-Tyr1]D-Tyr8]生长抑素具有高亲和力（Ka = 8.6 +/- 1.2 X 10(9) M-1），容量为54.4 +/- 2.6 fmol/mg。这些结合位点对天然肽及其活性类似物具有特异性，而其他肽激素，包括血管紧张素II、促甲状腺激素释放激素、抗利尿激素、催产素、P物质和促性腺激素释放激素，不抑制示踪剂的结合。几种生长抑素类似物的结合亲和力与它们作为大鼠垂体细胞生长激素释放抑制剂的效力之间存在良好的相关性。这些发现强调了垂体生长抑素受体在调节肽对生长激素释放的抑制作用中的生理重要性。使用Tyr1[d-Trp8]生长抑素作为标记配体，可以准确测定正常垂体中生长抑素受体的结合亲和力和浓度，为进一步研究生长抑素受体调控和受体介导的四肽细胞效应提供基础。
Somatostatin receptors in the rat pituitary gland were characterized by binding analysis with a radioiodinated high affinity somatostatin analogue, 125I-Tyr1[D-Trp8]somatostatin. Receptor binding of this derivative reached equilibrium at 30 min and was maintained at a plateau for at least 60 min. Two L-Trp8- labeled somatostatin analogues. 125I-Tyr1- and [125I-Tyr11]somatostatin, displayed less stable and lower specific uptake and higher nonspecific binding. In contrast to the rapid degradation of the L-Trp8 ligands during binding assay, 125I-Tyr1]D-Trp8]somatostatin retained more than 80% of its binding activity after 90 min of incubation with pituitary particles. Pituitary particles bound 125I-Tyr1]D-Tyr8]somatostatin with high affinity (Ka = 8.6 +/- 1.2 X 10(9) M-1) and capacity of 54.4 +/- 2.6 fmol/mg. These binding sites showed specificity for the native peptide and its active analogues, and other peptide hormones, including angiotensin II, thyrotropin-releasing hormone, vasopressin, oxytocin, substance P, and gonadotropin-releasing hormone, did not inhibit tracer binding. A good correlation was observed between the binding affinities of several somatostatin analogues and their potencies as inhibitors of growth hormone release in rat pituitary cells. These findings emphasize the physiological importance of the pituitary somatostatin receptor in mediating the inhibitory action of the peptide on growth hormone release. The use of Tyr1[d-Trp8]somatostatin as a labeled ligand permits accurate determinations of the binding affinity and concentration of receptors for somatostatin in the normal pituitary gland and provides a basis for further studies of somatostatin receptor regulation and receptor-mediated cellular effects of the tetradecapeptide.