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[3H] -去甲基鬼笔毒肽的肠道转运缺乏:在分离的小肠细胞和回肠刷状缘膜囊泡上与鬼笔毒素和胆汁酸的比较研究

Lack of intestinal transport of [3H]-demethylphalloin: comparative studies with phallotoxins and bile acids on isolated small intestinal cells and ileal brush border membrane vesicles.

作者信息

Petzinger E, Burckhardt G, Schwenk M, Faulstich H

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1982 Aug;320(2):196-200. doi: 10.1007/BF00506321.

Abstract

Several earlier studies suggested that the uptake of phallotoxins by liver cells is a carrier mediated process using a transport system normally handling bile acids (see Frimmer 1982). In this study we have shown whether ileal cells, well known to transport bile acids too, are able to take up phallotoxins. Isolated epithelial cells prepared from guinea pig ileum accumulated [14C]-cholate, whereas [3H]-demethylphalloin ([3H]-DMP) was not taken up. The same observation was made with isolated jejunal cells but the uptake of [14C]-cholate was much slower. [3H]-DMP, however, was partly bound to intestinal cells. This process was not inhibited by cholate, iodipamide, oligomycin and carbonylcyano-chlorophenylhydrazone (CCCP), compounds known to decrease the uptake of phallotoxins into liver cells. Substituting Na+ for choline+ and also Cl- for SCN- did not influence the binding of [3H]-DMP. Frozen intestinal cells from the guinea pig bound two time more [3H]-DMP after thawing compared with intact cells. Supplementary uptake experiments on isolated brush border membrane vesicles from rat ileum revealed that phalloidin does not inhibit taurocholate uptake and that taurocholate does not interfere with [3H]-DMP binding. The results suggest that [3H]-demethylphalloin is not recognized by the bile acid carrier of the guinea pig and the rat ileum. It is concluded that the transport system for bile acids present in ileal cell is different from that of liver cells.

摘要

早期的几项研究表明,肝细胞摄取鬼笔毒素是一个载体介导的过程,该过程利用了一个通常处理胆汁酸的转运系统(见弗里默,1982年)。在本研究中,我们探究了同样已知能够转运胆汁酸的回肠细胞是否能够摄取鬼笔毒素。从豚鼠回肠制备的分离上皮细胞积累了[14C] - 胆酸盐,而[3H] - 去甲基鬼笔环肽([3H] - DMP)未被摄取。对分离的空肠细胞也有相同的观察结果,但[14C] - 胆酸盐的摄取要慢得多。然而,[3H] - DMP部分与肠细胞结合。这一过程不受胆酸盐、碘番酸、寡霉素和羰基氰 - 对氯苯腙(CCCP)的抑制,这些化合物已知会减少鬼笔毒素进入肝细胞的摄取。用Na +替代胆碱 + 以及用Cl - 替代SCN - 均不影响[3H] - DMP的结合。与完整细胞相比,豚鼠冷冻肠细胞解冻后结合的[3H] - DMP多两倍。对大鼠回肠分离的刷状缘膜囊泡进行的补充摄取实验表明,鬼笔环肽不抑制牛磺胆酸盐的摄取,牛磺胆酸盐也不干扰[3H] - DMP的结合。结果表明,豚鼠和大鼠回肠的胆汁酸载体无法识别[3H] - 去甲基鬼笔环肽。得出的结论是,回肠细胞中存在的胆汁酸转运系统与肝细胞的不同。

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