Bruns C, Weckbecker G, Raulf F, Lübbert H, Hoyer D
Preclinical Research, SANDOZ Pharma AG, Basle, Switzerland.
Ciba Found Symp. 1995;190:89-101; discussion 101-10. doi: 10.1002/9780470514733.ch6.
Somatostatin regulates endocrine and exocrine secretion, possesses antiproliferative properties and acts as a neurotransmitter/neuromodulator in the central nervous system. These effects are mediated by G protein-coupled receptors, of which at least five types have been cloned (sstr1-5). In radioligand-binding studies we have compared the binding properties of sstr1-5 with their activities as somatostatin receptors. All receptors identified so far bind somatostatin-14 and somatostatin-28 with high affinity. The similarities in receptor sequence and in the binding profiles of short synthetic somatostastin analogues such as octreotide, MK 678 or RC 160 for sstr1-5 indicate the existence of two classes of receptors sstr1/sstr4 with virtually no or very low affinity and sstr2/sstr3/sstr5 with intermediate to high affinity for the short somatostatin analogues. All five receptors mediate inhibition of adenylyl cyclase; this inhibition is sensitive to pertussis toxin. In vitro and in vivo studies suggest the importance of sstr2 and/or sstr5 in the inhibition of growth hormone release. The sstr2 receptor is apparently the predominant subtype expressed in somatostatin receptor-positive tumours. Evidence exists for the importance of sstr5 receptors in insulin secretion and sstr1 receptors in oncology. Somatostatin receptor-selective agonists and antagonists will help to explore new therapeutic opportunities in oncology as well as in endocrine and gastrointestinal disorders and those of the central nervous system.
生长抑素调节内分泌和外分泌，具有抗增殖特性，并在中枢神经系统中作为神经递质/神经调质发挥作用。这些作用由G蛋白偶联受体介导，其中至少已克隆出五种类型（sstr1 - 5）。在放射性配体结合研究中，我们比较了sstr1 - 5的结合特性与其作为生长抑素受体的活性。目前鉴定出的所有受体均以高亲和力结合生长抑素 - 14和生长抑素 - 28。sstr1 - 5的受体序列以及诸如奥曲肽、MK 678或RC 160等短合成生长抑素类似物的结合谱的相似性表明存在两类受体，即对短生长抑素类似物亲和力极低或几乎没有的sstrl / sstr4，以及对其具有中等至高亲和力的sstr2 / sstr3 / sstr5。所有五种受体均介导腺苷酸环化酶的抑制作用；这种抑制作用对百日咳毒素敏感。体外和体内研究表明sstr2和/或sstr5在抑制生长激素释放方面的重要性。sstr2受体显然是生长抑素受体阳性肿瘤中表达的主要亚型。有证据表明sstr5受体在胰岛素分泌中以及sstr1受体在肿瘤学中具有重要性。生长抑素受体选择性激动剂和拮抗剂将有助于探索肿瘤学以及内分泌、胃肠道疾病和中枢神经系统疾病的新治疗机会。
