Green Adam K, Barnes David M, Karasov William H
Department of Wildlife Ecology, University of Wisconsin-Madison, 1630 Linden Dr., Madison, WI 53706, USA.
J Comp Physiol B. 2005 Jan;175(1):57-66. doi: 10.1007/s00360-004-0462-0. Epub 2004 Nov 25.
Permeability-glycoprotein (Pgp) actively exports numerous potentially toxic compounds once they diffuse into the cell membrane of intestinal epithelial cells. We adapted the everted sleeve technique to make the first measures of intestinal Pgp function in an avian species (chicken) and in wild mammalian species, and compared them to laboratory rats. Tissues maintained both structural and functional integrity, and our method offers advantages over other in vitro techniques by using smaller intestinal sections (1 cm), and shorter incubation times (8-12 min). To determine Pgp function, we compared accumulation of [(3)H]-digoxin in sleeves incubated in Ringer solution with and without a transport-saturating concentration of a competitive inhibitor, cyclosporin A. We demonstrated significant variation in Pgp activity within individuals along the intestine, between populations fed different diets, and between species (laboratory rats had one-third to one-fifth the Pgp activity of wild rodents). In chicken, we also tested the effect of natural metabolites on digoxin accumulation. We found that among flavonoids, genistein (200 microM), found in soy and other legumes, but not quercetin (10, 30, 100, 330 microM) or the 3-beta-glycoside isoquercetrin (100 microM), significantly increased digoxin accumulation. Among fungal metabolites, sterigmatocystin (5 microM), but not aflatoxin B1 (5 microM), significantly increased digoxin accumulation.
通透性糖蛋白（Pgp）一旦将许多潜在有毒化合物扩散到肠上皮细胞的细胞膜中，就会主动将其输出。我们采用外翻肠囊技术首次测量了鸟类（鸡）和野生哺乳动物物种的肠道Pgp功能，并将其与实验室大鼠进行了比较。组织保持了结构和功能的完整性，并且我们的方法通过使用较小的肠段（1厘米）和较短的孵育时间（8 - 12分钟），比其他体外技术具有优势。为了确定Pgp功能，我们比较了在含有和不含有竞争性抑制剂环孢菌素A的饱和转运浓度的林格溶液中孵育的肠囊中[³H] - 地高辛的积累情况。我们证明了个体沿肠道、不同饮食喂养的群体之间以及物种之间Pgp活性存在显著差异（实验室大鼠的Pgp活性是野生啮齿动物的三分之一到五分之一）。在鸡中，我们还测试了天然代谢产物对地高辛积累的影响。我们发现，在黄酮类化合物中，大豆和其他豆类中含有的染料木黄酮（200微摩尔），而不是槲皮素（10、30、100、330微摩尔）或3 - β -糖苷异槲皮苷（100微摩尔），显著增加了地高辛的积累。在真菌代谢产物中，柄曲霉素（5微摩尔），而不是黄曲霉毒素B1（5微摩尔），显著增加了地高辛的积累。
