Schneitler C, Kähler C, Wiedermann C J, Hogue-Angeletti R, Fischer-Colbrie R
Department of Pharmacology, University of Innsbruck, Austria.
J Neuroimmunol. 1998 Jun 1;86(1):87-91. doi: 10.1016/s0165-5728(98)00012-5.
Secretoneurin (SN) is a novel neuropeptide expressed in the central and peripheral nervous system as well as in various endocrine tissues. SN inhibits growth of aortic pulmonary and endothelial cells and is a potent chemoattractant for endothelial cells, skin fibroblasts and monocytes. We investigated here the presence of specific high affinity binding sites for SN on a target tissue. SN was iodinated with the Bolton-Hunter (BH) reagent and purified by isocratic reversed phase chromatography. Specific binding sites for 125I-BHSN were identified on human Mono Mac 6 cells, a monocytic cell line. Scatchard analysis revealed a single class of binding sites with a Kd value of 7.3 nM and a Bmax of 322 (fmol/mg protein). Competition studies demonstrated that the 15 C-terminal amino acids of SN could displace authentic SN, whereas shorter fragments were inactive. Other sensory neuropeptides like substance P, calcitonin gene-related peptide or galanin as well as the chemokine receptor ligand Rantes or the typical chemoattractant FMLP could not displace SN. Our studies demonstrate specific high affinity binding sites for SN on a monocytic cell line. Since SN exerts a potent chemotactic activity towards monocytes and increases cytosolic calcium in these cells, these binding sites might well represent a putative functional plasma membrane receptor for SN.
分泌神经肽(SN)是一种新型神经肽,在中枢和外周神经系统以及各种内分泌组织中表达。SN可抑制主动脉肺细胞和内皮细胞的生长,并且是内皮细胞、皮肤成纤维细胞和单核细胞的有效趋化剂。我们在此研究了目标组织上SN的特异性高亲和力结合位点的存在情况。用博尔顿-亨特(BH)试剂对SN进行碘化,并通过等度反相色谱法进行纯化。在人单核细胞系Mono Mac 6细胞上鉴定出了125I-BHSN的特异性结合位点。斯卡查德分析显示存在一类结合位点,其解离常数(Kd)值为7.3 nM,最大结合容量(Bmax)为322(fmol/mg蛋白质)。竞争研究表明,SN的15个C末端氨基酸可以取代天然SN,而较短的片段则无活性。其他感觉神经肽如P物质、降钙素基因相关肽或甘丙肽,以及趋化因子受体配体RANTES或典型的趋化剂N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸(FMLP)都不能取代SN。我们的研究证明了在单核细胞系上存在SN的特异性高亲和力结合位点。由于SN对单核细胞具有强大的趋化活性并增加这些细胞中的胞质钙,这些结合位点很可能代表了SN的一种假定功能性质膜受体。