Quik M, Babu U, Audhya T, Goldstein G
Department of Pharmacology, McGill University, Montreal, Quebec, Canada.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2603-7. doi: 10.1073/pnas.88.6.2603.
Thymopoietin, a polypeptide hormone of the thymus that has pleiotropic actions on the immune, endocrine, and nervous systems, potently interacts with the neuromuscular nicotinic acetylcholine receptor. Thymopoietin binds to the nicotinic alpha-bungarotoxin (alpha-BGT) receptor in muscle and, like alpha-BGT, inhibits cholinergic transmission at this site. Evidence is given that radiolabeled thymopoietin similarly binds to a nicotinic alpha-BGT-binding site within the brain and does so with the characteristics of a specific receptor ligand. Thus specific binding to neuronal membranes was saturable, of high affinity (Kd = 8 nM), linear with increased tissue concentration, and readily reversible; half-time was approximately 5 min for association and 10 min for dissociation. Binding of 125I-labeled thymopoietin was displaced not only by unlabeled thymopoietin but also by alpha-BGT and the nicotinic receptor ligands d-tubocurarine and nicotine; various other receptor ligands (muscarinic, adrenergic, and dopaminergic) did not affect binding of 125I-labeled thymopoietin. Thymopoietin was shown by ELISA to be present in brain extracts, displacement curves of thymus and brain extracts being parallel to the standard thymopoietin curve, and Western (immuno) blot identified in brain and thymus extracts a thymopoietin-immunoreactive polypeptide of the same molecular mass as purified thymopoietin polypeptide. We conclude that thymopoietin and thymopoietin-binding sites are present within the brain and that the receptor for thymopoietin is the previously identified nicotinic alpha-BGT-binding site of neuronal tissue.
胸腺生成素是一种胸腺多肽激素，对免疫、内分泌和神经系统具有多效性作用，它能与神经肌肉烟碱型乙酰胆碱受体发生强烈相互作用。胸腺生成素与肌肉中的烟碱型α-银环蛇毒素（α-BGT）受体结合，并且与α-BGT一样，抑制该部位的胆碱能传递。有证据表明，放射性标记的胸腺生成素同样能与脑内的烟碱型α-BGT结合位点结合，且具有特异性受体配体的特征。因此，与神经元膜的特异性结合是可饱和的，具有高亲和力（Kd = 8 nM），随组织浓度增加呈线性关系，且易于逆转；结合半衰期约为5分钟，解离半衰期约为10分钟。125I标记的胸腺生成素的结合不仅能被未标记的胸腺生成素取代，还能被α-BGT以及烟碱型受体配体d-筒箭毒碱和尼古丁取代；其他各种受体配体（毒蕈碱型、肾上腺素能和多巴胺能）均不影响125I标记的胸腺生成素的结合。通过酶联免疫吸附测定法（ELISA）显示脑提取物中存在胸腺生成素，胸腺提取物和脑提取物的置换曲线与标准胸腺生成素曲线平行，蛋白质免疫印迹法（Western blot）在脑提取物和胸腺提取物中鉴定出一种与纯化的胸腺生成素多肽分子量相同的胸腺生成素免疫反应性多肽。我们得出结论，脑内存在胸腺生成素及其结合位点，并且胸腺生成素的受体是先前确定的神经元组织的烟碱型α-BGT结合位点。
