Hannon Jason P, Nunn Caroline, Stolz Barbara, Bruns Christians, Weckbecker Gisbert, Lewis Ian, Troxler Thomas, Hurth Konstanze, Hoyer Daniel
Nervous System, Novartis Pharma AG, Basel, Switzerland.
J Mol Neurosci. 2002 Feb-Apr;18(1-2):15-27. doi: 10.1385/JMN:18:1-2:15.
Somatostatin (SRIF, somatotropin release inhibiting factor), discovered for its inhibitory action on growth hormone (GH) secretion from pituitary, is an abundant neuropeptide. Two forms, SRIF14 and SRIF28 exist. Recently, a second family of peptides with very similar sequences and features was described; the cortistatins (CST), CST17 and CST29 which are brain selective. The five cloned SRIF receptors (sst1-5) belong to the G-protein coupled/ heptathelical receptor family. Structural and operational features distinguish two classes of receptors; SRIF1 - sst2/sst3/sst5 (high affinity for octreotide or seglitide) and SRIF2 = sst1/sst4(very low affinitty for the aforementioned ligands). The affinity of SRIF receptors for somatostatins and cortistatins is equally high, and it is not clear whether selective receptors do exist for one or the other of the peptides. Several radiologlands label all SRIF receptors, e.g., [125]LTT-SRIF28' [l25I]CGP23996, [125]Tyr10cortistatin or [125I]Tyr11SRIF14. In contrast, [125I]Tyr3octreotide, [125I]BIM23027, [125I]MK678 or [125I]D-Trp8SRIF14 label predominantly SRIF1 sites, especially sst2 and possibly sst5 receptors. In brain, [125I]Tyr3octreotide binding equates with sst2 receptor mRNA distribution. Native SRIF2receptors can be labeled with [125I]SRIF14 in the presence of high NaCl in brain (sst1) or lung (sst4) tissue. Short cyclic or linear peptide analogs show selectivity for sst2/sst5 (octreotide, lanreotide, BIM 23027), sst1 (CH-275), sst3 (sst3-ODN-8), or sst5 receptors (BIM 23268); although claims for selectivity have not always been confirmed. Beta peptides ith affinity for SRIF receptors are also reported. The general lack of SRIF receptor antagonists is unique for peptide receptors, although CYN 154806 is a selective and potent sst2 antagonist. Nonpeptide ligands are still rare, although a number of molecules have been reported with selectivity and potency for sst1 (L 757,519), sst2 (L 779,976), sst3 (L 796,778), sst4 (NNC 26-9100, L 803,087) or sst1/sst5 receptors (L 817,018). Such molecules are essential to establish the role of SRIF receptors, e.g., sst1 in hypothalamic glutamate currents: sst2 in inhibiting release of GH, glucagon, TSH, gastric acid secretion, pain, seizures and tumor growth, and sst5 in vascular remodeling and inhibition of insulin and GH release.
生长抑素（SRIF，促生长素释放抑制因子）因对垂体生长激素（GH）分泌具有抑制作用而被发现，是一种广泛存在的神经肽。它有两种形式，即SRIF14和SRIF28。最近，人们发现了另一类序列和特性非常相似的肽；即脑选择性的促肾上腺皮质激素释放抑制因子（CST），CST17和CST29。已克隆出的五种SRIF受体（sst1 - 5）属于G蛋白偶联/七螺旋受体家族。结构和功能特性区分出两类受体；SRIF1 = sst2/sst3/sst5（对奥曲肽或司美格鲁肽具有高亲和力）和SRIF2 = sst1/sst4（对上述配体亲和力极低）。SRIF受体对生长抑素和促肾上腺皮质激素释放抑制因子的亲和力同样高，目前尚不清楚是否存在对其中一种肽具有选择性的受体。几种放射性配体可标记所有SRIF受体，例如，[125I]LTT - SRIF28、[125I]CGP23996、[125I]Tyr10促肾上腺皮质激素释放抑制因子或[125I]Tyr11SRIF14。相比之下，[125I]Tyr3奥曲肽、[125I]BIM23027、[125I]MK678或[125I]D - Trp8SRIF14主要标记SRIF1位点，尤其是sst2，可能还有sst5受体。在脑中，[125I]Tyr3奥曲肽结合与sst2受体mRNA分布一致。在脑（sst1）或肺（sst4）组织中，在高浓度氯化钠存在的情况下，天然SRIF2受体可用[125I]SRIF14标记。短环肽或线性肽类似物对sst2/sst5（奥曲肽、兰瑞肽、BIM 23027）、sst1（CH - 275）、sst3（sst3 - ODN - 8）或sst5受体（BIM 23268）具有选择性；尽管对选择性的说法并非总能得到证实。也有报道称存在对SRIF受体具有亲和力的β肽。肽受体普遍缺乏SRIF受体拮抗剂，不过CYN 154806是一种选择性且强效的sst2拮抗剂。非肽类配体仍然很少见，尽管已有一些分子被报道对sst1（L 757,519）、sst2（L 779,976）、sst3（L 796,778）、sst4（NNC 26 - 9100、L 803,087）或sst1/sst5受体（L 817,018）具有选择性和活性。这类分子对于确定SRIF受体的作用至关重要，例如，sst1在下丘脑谷氨酸电流中的作用；sst2在抑制GH、胰高血糖素、促甲状腺激素释放、胃酸分泌、疼痛、癫痫发作和肿瘤生长方面的作用，以及sst5在血管重塑和抑制胰岛素及GH释放方面的作用。
