Laburthe M, Couvineau A, Amiranoff B, Voisin T
Inserm V239, Faculté de Médecine, Bichat, Paris, France.
Baillieres Clin Endocrinol Metab. 1994 Jan;8(1):77-110. doi: 10.1016/s0950-351x(05)80227-7.
Receptors for regulatory peptides (hormones or neurotransmitters) play a pivotal role in the ability of cells to taste the rich neuroendocrine environment of the gut. Recognition of low concentration of peptides with a high specificity and translation of the peptide-receptor interaction into a biological response through different signalling pathways (adenylyl cyclase-cAMP or phospholipase C-phosphatidylinositol) are crucial properties of receptors. While many new receptors have been identified and thereafter characterized functionally during the 1980s, molecular biology now emerges as the privileged way for the structural characterization and discovery of receptors. Different strategies of receptor cloning have been developed which may or may not require prior receptor purification. Among cloning strategies that do not require receptor purification, homology screening of cDNA libraries, expression of receptor cDNA or mRNA in Xenopus laevis oocytes or in COS cells, and the polymerase chain reaction method achieved great success, e.g. cloning of receptors for cholecystokinin, gastrin, glucagon-like peptide 1, gastrin-releasing peptide/bombesin, neuromedin K, neuropeptide Y, neurotensin, opioids, secretin, somatostatin, substance K, substance P and vasoactive intestinal peptide. All these receptors belong to the superfamily of G-protein-coupled receptors which consist of a single polypeptide chain (350-450 amino acids) with seven transmembrane segments, an N-terminal extracellular domain and a C-terminal cytoplasmic domain. In this chapter, we have detailed the properties of three receptors which play an important role in digestive tract physiology and illustrate various signal transduction pathways: pancreatic beta-cell galanin receptors which mediate inhibition of insulin release and intestinal epithelial receptors for vasoactive intestinal peptide and peptide YY, which mediate the stimulation and inhibition of water and electrolyte secretion, respectively.
调节肽（激素或神经递质）受体在细胞感知肠道丰富神经内分泌环境的能力中起关键作用。以高特异性识别低浓度肽，并通过不同信号通路（腺苷酸环化酶 - cAMP或磷脂酶C - 磷脂酰肌醇）将肽 - 受体相互作用转化为生物学反应，是受体的关键特性。虽然在20世纪80年代已经鉴定出许多新受体并对其进行了功能表征，但分子生物学现在已成为受体结构表征和发现的优先方法。已经开发了不同的受体克隆策略，这些策略可能需要也可能不需要事先纯化受体。在不需要受体纯化的克隆策略中，cDNA文库的同源性筛选、受体cDNA或mRNA在非洲爪蟾卵母细胞或COS细胞中的表达以及聚合酶链反应方法都取得了巨大成功，例如胆囊收缩素、胃泌素、胰高血糖素样肽1、胃泌素释放肽/蛙皮素、神经介素K、神经肽Y、神经降压素、阿片类物质、促胰液素、生长抑素、物质K、P物质和血管活性肠肽的受体克隆。所有这些受体都属于G蛋白偶联受体超家族，该家族由具有七个跨膜区段的单条多肽链（350 - 450个氨基酸）、一个N端细胞外结构域和一个C端细胞质结构域组成。在本章中，我们详细介绍了在消化道生理学中起重要作用的三种受体的特性，并说明了各种信号转导途径：介导胰岛素释放抑制的胰腺β细胞甘丙肽受体，以及分别介导水和电解质分泌刺激和抑制的血管活性肠肽和肽YY的肠上皮受体。
