Division of Endocrinology and Metabolism, Department of Medicine and Department of Physiology and Biophysics (MB), State University of New York at Stony Brook, Stony Brook, New York 11794.
Mol Cell Neurosci. 1993 Jun;4(3):245-9. doi: 10.1006/mcne.1993.1031.
Somatostatin (SS14) is an important regulator of endocrine and brain function exerting its action after binding to high-affinity membrane receptor subtypes. Its diverse physiological activities include inhibition of hormone secretion from pituitary, pancreas, and gut. In the CNS, SS14 acting as a neurotransmitter/neuromodulator exerts inhibitory effects on neural function. Recently, three SS14 receptor genes, SSTR1, SSTR2, and SSTR3, have been cloned and characterized. We have cloned and characterized a novel fourth member of this gene family from a rat genomic library, SSTR4, which is expressed predominantly in neural tissue. When stably expressed in CHO-K1 cells, SSTR4 binds SS14 and SS28 with high affinity; however, the SS14 analogs SMS 201-995 and MK 678 failed to displace specific binding. High-affinity agonist binding was diminished by prior exposure to both GTPgammaS and pertussis toxin (PTX) but was not effected following agonist pretreatment, indicating that SSTR4 is coupled to a PTX-sensitive G-protein but does not desensitize. SSTR4 expressed in CHO cells is coupled by a PTX-sensitive G-protein to inhibition of adenylyl cyclase since treatment of transfected cells with SS14 resulted in the inhibition of forskolin-stimulated cAMP accumulation, an effect that was abolished by PTX treatment. The cloning of four SS14 receptor subtypes provide molecular probes for structure-function studies and for identifying those particular subtypes responsible for mediating the diverse physiological action of SS14.
生长抑素（SS14）是一种重要的内分泌和大脑功能调节剂，通过与高亲和力的膜受体亚型结合发挥作用。其多样的生理活性包括抑制垂体、胰腺和肠道的激素分泌。在中枢神经系统中，SS14 作为神经递质/神经调质，对神经功能发挥抑制作用。最近，已经克隆和鉴定了三种 SS14 受体基因，SSTR1、SSTR2 和 SSTR3。我们从大鼠基因组文库中克隆和鉴定了该基因家族的一个新成员 SSTR4，其主要在神经组织中表达。当在 CHO-K1 细胞中稳定表达时，SSTR4 与 SS14 和 SS28 具有高亲和力结合；然而，SS14 类似物 SMS 201-995 和 MK 678 不能置换特异性结合。高亲和力激动剂结合在预先暴露于 GTPγS 和百日咳毒素（PTX）后减少，但在激动剂预处理后不受影响，表明 SSTR4 与 PTX 敏感的 G 蛋白偶联，但不脱敏。在 CHO 细胞中表达的 SSTR4 通过 PTX 敏感的 G 蛋白偶联，抑制腺苷酸环化酶，因为 SS14 处理转染细胞导致 forskolin 刺激的 cAMP 积累受到抑制，该作用被 PTX 处理所消除。四种 SS14 受体亚型的克隆为结构功能研究提供了分子探针，并确定了介导 SS14 多种生理作用的特定亚型。
