London R M, Krause W J, Fan X, Eber S L, Forte L R
Truman Veterans Affairs Medical Center, Columbia, Missouri 65212, USA.
Am J Physiol. 1997 Jul;273(1 Pt 1):G93-105. doi: 10.1152/ajpgi.1997.273.1.G93.
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.
鸟苷林和尿鸟苷林是激活受体鸟苷酸环化酶（GCs）并引起肠道分泌增加的肽。导致旅行者腹泻的细菌产生模仿这种作用的热稳定毒素（STs）。对大鼠胃肠道中受体GCs的分布和特性进行的研究表明，这些受体定位于胃和肠道的上皮细胞。胃黏膜中的细胞簇以及肠道内衬的肠细胞表现出对125I标记的ST的特异性结合。用腔内ST处理的胃和肠的结扎肠袢中，鸟苷3',5'-环磷酸（cGMP）显著增加，十二指肠的反应最为明显。在胃和肠道中均发现了鸟苷酸环化酶C（GCC）mRNA和一种截短的、类似GCC的mRNA。两种mRNA均作为编码GC催化结构域的cDNA被分离出来。0.9千碱基（kb）的cDNA与GCC的同源性为99.8%，而截短的0.75-kb类似GCC的cDNA有一个159个核苷酸的缺失，在蛋白质水平上与GCC的同源性为96.6%。在胃和肠道中检测到了尿鸟苷林和鸟苷林mRNA。尿鸟苷林mRNA在小肠中最为丰富，而鸟苷林mRNA在大肠中含量最高。因此，胃和肠道是鸟苷林和尿鸟苷林通过cGMP调节转运的靶器官。
