Signal transduction pathways via guanylin and uroguanylin in stomach and intestine.
Signal transduction pathways via guanylin and uroguanylin in stomach and intestine.
复制标题
胃和肠中通过鸟苷蛋白和尿鸟苷蛋白的信号转导途径。
作者：
R. London;W. Krause;X. Fan;S. Eber;L. Forte
鸟苷素和尿鸟苷素是激活受体鸟苷酸环化酶（GC）并引起肠分泌增加的肽。引起旅行者腹泻的细菌产生模拟这种作用的热稳定毒素（ST）。对受体GC在大鼠胃肠道中的分布和特性的研究表明，受体定位于胃和肠的上皮细胞。在胃粘膜和肠上皮细胞内衬肠的细胞簇表现出特异性结合的125 I-标记的ST。结扎环的胃和肠腔内ST治疗有显着增加鸟苷3 '，5'-环磷酸（cGMP），与十二指肠表现出最大的反应。鸟苷酸环化酶C（GCC）的mRNA和截短，GCC样mRNA的表达被发现在胃和肠。两种mRNA均分离为编码GC催化结构域的cDNA。0.9-kb的cDNA与GCC的同源性为99.8%，而截短的0.75-kb的GCC样cDNA具有159个核苷酸的缺失，在蛋白质水平上与GCC的同源性为96.6%。在胃和肠中检测到尿鸟苷素和鸟苷素mRNA。尿鸟苷素mRNA在小肠中含量最高，而鸟苷素mRNA在大肠中含量最高。因此，胃和肠是鸟苷素和尿鸟苷素通过cGMP调节转运的靶标。
Guanylin and uroguanylin are peptides that activate receptor guanylate cyclases (GCs) and elicit increased intestinal secretion. Bacteria that cause traveler's diarrhea produce heat-stable toxins (STs) that mimic this action. Investigation of the distribution and identity of receptor GCs in the gastrointestinal tract of rats revealed that receptors were localized to epithelial cells in stomach and intestine. Clusters of cells in gastric mucosa and enterocytes lining the intestine exhibited specific binding of 125I-labeled ST. Ligated loops of stomach and intestine treated with intraluminal ST had significant increases in guanosine 3',5'-cyclic monophosphate (cGMP), with duodenum exhibiting the greatest response. Expression of guanylate cyclase C (GCC) mRNA and a truncated, GCC-like mRNA was found in both stomach and intestine. Both mRNAs were isolated as cDNAs encoding the GC catalytic domain. The 0.9-kilobase (kb) cDNA is 99.8% identical to GCC, whereas the truncated, 0.75-kb GCC-like cDNA has a 159-nucleotide deletion and is 96.6% identical to GCC at the protein level. Uroguanylin and guanylin mRNAs were detected in stomach and intestine. Uroguanylin mRNA was most abundant in small intestine, whereas guanylin mRNA was highest in large intestine. Thus the stomach and intestine are targets for regulation of transport by guanylin and uroguanylin via cGMP.