Krause W J, Freeman R H, Eber S L, Hamra F K, Fok K F, Currie M G, Forte L R
Department of Pathology and Anatomical Sciences, University of Missouri, Columbia 65212, USA.
Acta Anat (Basel). 1995;153(3):210-9. doi: 10.1159/000147735.
Pathogenic strains of enteric bacteria secrete small heat-stable toxins (STs) that activate membrane guanylyl cyclase receptors found in the intestine. The intestinal peptide agonists, guanylin and uroguanylin, are structurally related to STs. Receptors for 125I-ST were found throughout the entire length of the intestinal tract of all the birds examined. These receptors were restricted to intestinal epithelial cells covering villi and forming intestinal glands and were not observed in other strata of the gut wall. The most intense labeling of receptors by 125I-ST occurred in the region of the microvillus border of individual enterocytes. There appeared to be a decrease in receptor density distally along the length of the small intestine, although labeling of receptors by 125I-ST was observed throughout the small intestine and colon. Cellular cGMP accumulation responses to Escherichia coli ST and rat guanylin in the domestic turkey and duck were greater in the proximal small intestine compared to the distal small intestine or colon. Brush border membranes (BBM) isolated from the mucosa of proximal small intestine of turkeys exhibited agonist-stimulated guanylyl cyclase activity. The rank order potency for enzyme activation was E. coli ST > uroguanylin > guanylin. Competitive radioligand binding assays using 125I-ST and turkey intestine BBM revealed a similar rank order affinity for the receptors that was exemplified by the Kd values of ST 2.5 nM, uroguanylin 80 nM and guanylin 2.6 microM. It may be concluded that functional receptors for the endogenous peptides, guanylin and uroguanylin, occur in the apical membranes of enterocytes throughout the avian intestine. The receptor-guanylyl cyclase(s) of proximal small intestine were preferentially activated by uroguanylin relative to guanylin, but both endogenous peptides were less potent than their molecular mimic, E. coli ST.
肠道细菌的致病菌株分泌小的热稳定毒素（STs），这些毒素可激活肠道中发现的膜鸟苷酸环化酶受体。肠道肽激动剂鸟苷素和尿鸟苷素在结构上与STs相关。在所有被检查鸟类的整个肠道中都发现了125I-ST的受体。这些受体仅限于覆盖绒毛并形成肠腺的肠上皮细胞，在肠壁的其他层中未观察到。125I-ST对受体的标记最强烈的部位出现在单个肠细胞的微绒毛边界区域。尽管在整个小肠和结肠中都观察到125I-ST对受体的标记，但沿小肠长度向远端受体密度似乎有所降低。与远端小肠或结肠相比，家火鸡和鸭近端小肠对大肠杆菌ST和大鼠鸟苷素的细胞cGMP积累反应更大。从火鸡近端小肠黏膜分离的刷状缘膜（BBM）表现出激动剂刺激的鸟苷酸环化酶活性。酶激活的效价顺序为：大肠杆菌ST＞尿鸟苷素＞鸟苷素。使用125I-ST和火鸡肠BBM进行的竞争性放射性配体结合试验显示，受体的亲和力顺序相似，其Kd值分别为：ST 2.5 nM、尿鸟苷素80 nM和鸟苷素2.6 μM。可以得出结论，内源性肽鸟苷素和尿鸟苷素的功能性受体存在于整个鸟类肠道肠细胞的顶端膜中。相对于鸟苷素，近端小肠的受体-鸟苷酸环化酶优先被尿鸟苷素激活，但这两种内源性肽的效力均低于它们的分子模拟物大肠杆菌ST。
