Fan X, Wang Y, London R M, Eber S L, Krause W J, Freeman R H, Forte L R
The Truman Veterans Administration Medical Center, Department of Pharmacology, Missouri University School of Medicine, Columbia 65212, USA.
Endocrinology. 1997 Nov;138(11):4636-48. doi: 10.1210/endo.138.11.5539.
Guanylin and uroguanylin are peptides that stimulate membrane guanylate cyclases (GC) and regulate intestinal and renal function via cGMP. Complementary DNAs were isolated encoding opossum preproguanylin and a 279-amino acid portion of a receptor-guanylate cyclase expressed in opossum kidney (OK) cells (GC-OK). The tissue expression of messenger RNA transcripts for these signaling molecules were then compared. Northern and/or reverse transcription-PCR assays revealed that guanylin, uroguanylin, and GC-OK messenger RNAs are expressed in tissues within the digestive, renal, central nervous, reproductive, and lymphoid organ systems. Receptor autoradiography localized the receptors for uroguanylin and guanylin to renal proximal tubules and seminiferous tubules of testis. Synthetic guanylin and uroguanylin peptides activated the receptor-GCs in opossum kidney cortex and in cultured OK cells eliciting increased intracellular cGMP. Expression of agonist and receptor-GC signaling molecules provides a pathway for paracrine and/or autocrine regulation of cellular functions via cGMP in the digestive, renal, central nervous, reproductive, and lymphoid/immune organ systems. Uroguanylin also links the intestine and kidney in a potential endocrine axis that activates tubular receptor-GCs and influences renal function.
鸟苷林和尿鸟苷林是刺激膜鸟苷酸环化酶（GC）并通过环磷酸鸟苷（cGMP）调节肠道和肾功能的肽。分离出了编码负鼠前体鸟苷林的互补DNA以及在负鼠肾（OK）细胞中表达的一种受体鸟苷酸环化酶（GC-OK）的279个氨基酸的片段。然后比较了这些信号分子的信使核糖核酸（mRNA）转录本的组织表达情况。Northern印迹法和/或逆转录-聚合酶链反应（RT-PCR）分析显示，鸟苷林、尿鸟苷林和GC-OK的mRNA在消化、肾脏、中枢神经、生殖和淋巴器官系统的组织中均有表达。受体放射自显影将尿鸟苷林和鸟苷林的受体定位到肾近端小管和睾丸的生精小管。合成的鸟苷林和尿鸟苷林肽激活了负鼠肾皮质和培养的OK细胞中的受体-GC，导致细胞内cGMP增加。激动剂和受体-GC信号分子的表达提供了一条通过cGMP在消化、肾脏、中枢神经、生殖和淋巴/免疫器官系统中对细胞功能进行旁分泌和/或自分泌调节的途径。尿鸟苷林还在一个潜在的内分泌轴中连接肠道和肾脏，该轴激活肾小管受体-GC并影响肾功能。
