Forte L R, Eber S L, Fan X, London R M, Wang Y, Rowland L M, Chin D T, Freeman R H, Krause W J
Harry S. Truman Memorial Veterans' Hospital, Department of Pharmacology, School of Medicine, Missouri University, Columbia 65212, USA.
Endocrinology. 1999 Apr;140(4):1800-6. doi: 10.1210/endo.140.4.6630.
Guanylin and uroguanylin are small peptides containing two disulfide bonds that activate membrane guanylate cyclase-receptors in the intestine, kidney and other epithelia. Hybridization assays with a uroguanylin complementary DNA (cDNA) detected uroguanylin-like messenger RNAs (mRNAs) in the opossum spleen and testis, but these transcripts are larger than uroguanylin mRNAs. RT of RNA from spleen to produce cDNAs for amplification in the PCR followed by cloning and sequencing revealed a novel lymphoid-derived cDNA containing an open reading frame encoding a 109-amino acid polypeptide. This protein shares 84% and 40% of its residues with preprouroguanylin and preproguanylin, respectively. A 15-amino acid, uroguanylin-like peptide occurs at the COOH-terminus of the precursor polypeptide. However, this peptide is unique in having only three cysteine residues. We named the gene and its peptide product lymphoguanylin because the source of the first cDNA isolated was spleen and its mRNA is expressed in all of the lymphoid tissues tested. A 15-amino acid form of lymphoguanylin containing a single disulfide bond was synthesized that activates the guanylate cyclase receptors of human T84 intestinal and opossum kidney (OK) cells, although with less potency than uroguanylin and guanylin. Northern and/or RT-PCR assays detected lymphoguanylin mRNA transcripts in many tissues and organs of opossums, including those within the lymphoid/immune, cardiovascular/renal, reproductive, and central nervous organ systems. Lymphoguanylin joins guanylin and uroguanylin in a growing family of peptide agonists that activate transmembrane guanylate cyclase receptors, thus influencing target cell function via the intracellular second messenger, cGMP.
鸟苷林和尿鸟苷林是含有两个二硫键的小肽，可激活肠道、肾脏和其他上皮组织中的膜鸟苷酸环化酶受体。用尿鸟苷林互补DNA（cDNA）进行杂交分析，在负鼠脾脏和睾丸中检测到了类似尿鸟苷林的信使核糖核酸（mRNA），但这些转录本比尿鸟苷林mRNA大。从脾脏提取RNA进行逆转录以产生用于PCR扩增的cDNA，随后进行克隆和测序，发现了一种新的淋巴来源的cDNA，其含有一个编码109个氨基酸多肽的开放阅读框。该蛋白质分别与前尿鸟苷林原和前鸟苷林原共有84%和40%的氨基酸残基。一个15个氨基酸的、类似尿鸟苷林的肽出现在前体多肽的COOH末端。然而，该肽的独特之处在于仅含有三个半胱氨酸残基。我们将该基因及其肽产物命名为淋巴鸟苷林，因为分离出的第一个cDNA的来源是脾脏，且其mRNA在所有检测的淋巴组织中均有表达。合成了一种含有单个二硫键的15个氨基酸形式的淋巴鸟苷林，它可激活人T84肠道细胞和负鼠肾脏（OK）细胞的鸟苷酸环化酶受体，尽管其效力低于尿鸟苷林和鸟苷林。Northern印迹法和/或逆转录-聚合酶链反应（RT-PCR）分析在负鼠的许多组织和器官中检测到了淋巴鸟苷林mRNA转录本，包括淋巴/免疫系统、心血管/肾脏系统、生殖系统和中枢神经系统内的组织和器官。淋巴鸟苷林与鸟苷林和尿鸟苷林一起，成为一个不断扩大的肽激动剂家族，这些激动剂可激活跨膜鸟苷酸环化酶受体，从而通过细胞内第二信使环磷酸鸟苷（cGMP）影响靶细胞功能。
