Kunzelmann Karl, Sun J, Schreiber R, König Jens
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.
Br J Pharmacol. 2004 Aug;142(8):1219-26. doi: 10.1038/sj.bjp.0705857. Epub 2004 Jul 5.
Phytohemagglutinins are widely distributed in common food items. They constitute a heterogeneous group of proteins, which are often resistant to proteolysis in the gastrointestinal tract. Upon binding to the luminal membrane of intestinal cells, they can interfere with digestive, protective or secretory functions of the intestine. Phytohemagglutinins present in red kidney beans and jackbeans have been shown to induce diarrhea and hypersecretion in human airways, but the underlying mechanisms remain obscure. We examined how agglutinins from wheat germ (WGA), soy bean (SBA), red kidney beans (Pha-E, Pha-L), and jackbeans (Con-A) affect ion transport in mouse airways and large intestine using Ussing chamber techniques. We found that Pha-E, Pha-L, and Con-A but not WGA and SBA inhibit electrogenic Na(+) absorption dose dependently in both colon and trachea. The inhibitory effects of Con-A on Na(+) absorption were suppressed by the sugar mannose, by inhibition of phospholipase C (PLC) and protein kinase C (PKC). Thus, nutritional phytohemagglutinins block salt absorption in a PLC- and PKC-dependent manner, probably by inhibition of the epithelial Na(+) channel (ENaC). This effect may be therapeutically useful in patients suffering from cystic fibrosis.
植物血凝素广泛分布于常见食物中。它们是一类异质性蛋白质,通常在胃肠道中对蛋白水解具有抗性。与肠道细胞的腔面膜结合后,它们会干扰肠道的消化、保护或分泌功能。已证实红芸豆和刀豆中的植物血凝素可导致人类气道腹泻和分泌过多,但潜在机制仍不清楚。我们使用尤斯灌流小室技术研究了来自小麦胚芽(WGA)、大豆(SBA)、红芸豆(Pha-E、Pha-L)和刀豆(Con-A)的凝集素如何影响小鼠气道和大肠中的离子转运。我们发现Pha-E、Pha-L和Con-A而非WGA和SBA在结肠和气管中均剂量依赖性地抑制电中性Na(+)吸收。Con-A对Na(+)吸收的抑制作用可被糖类甘露糖、通过抑制磷脂酶C(PLC)和蛋白激酶C(PKC)所抑制。因此,营养性植物血凝素可能通过抑制上皮Na(+)通道(ENaC)以PLC和PKC依赖的方式阻断盐吸收。这种效应在患有囊性纤维化的患者中可能具有治疗作用。