The present study was aimed at kinetically characterizing the newly found carrier-mediated riboflavin transport system in the rat colon, comparing it with that in the small intestine, and also probing the potential roles of these transport systems in intestinal drug absorption. Riboflavin transport, evaluated by measuring the initial uptake into everted intestinal tissue sacs, was saturable with a Michaelis constant (Km) of 0.13 microM and a maximum transport rate (Jmax) of 0.74 pmol/min/100 mg wet tissue weight (wtw) in the colon. Both the Km and the Jmax were smaller than those (0.57 microM and 4.26 pmol/min/100 mg wtw, respectively) in the small intestine, suggesting that the transport system in the colon has a higher affinity to substrates and a smaller transport capacity than its counterpart in the small intestine. The carrier-mediated riboflavin transport in the colon, similarly to that in the small intestine, was Na+-dependent and inhibited by lumiflavin, a riboflavin analogue with an isoalloxazine ring, but not by D-ribose, which forms the side-chain attached to the isoalloxazine ring in riboflavin. To further clarify the substrate specificities of the transport systems, we examined the effects of several drugs with a tricyclic structure similar to isoalloxazine ring on riboflavin transport. Chlorpromazine, a phenothiazine derivative, was found to inhibit riboflavin transport in both the small intestine and the colon. Methylene blue also was found to be a potent inhibitor in both sites. These results suggest that some tricyclic-type drugs could interfere with intestinal riboflavin absorption by specific carrier-mediated transport systems. These transport systems may play roles in the absorption of tricyclic-type drugs.

译文

:本研究旨在动力学表征大鼠结肠中新发现的载体介导的核黄素转运系统,将其与小肠中的核黄素转运系统进行比较,并探讨这些转运系统在肠道药物吸收中的潜在作用。核黄素转运是通过测量肠外翻组织囊的初始吸收来评估的,其饱和度(米氏常数)(Km)为0.13 microM,最大转运速率(Jmax)为0.74 pmol / min / 100 mg湿组织重量(wtw)。冒号。 Km和Jmax均小于小肠中的Km和Jmax(分别为0.57 microM和4.26 pmol / min / 100 mg wtw),这表明结肠中的转运系统与底物的亲和力更高,转运能力比它在小肠中的对应物。载体介导的核黄素在结肠中的转运与小肠中的转运类似,是Na依赖性的,并受到lumiflavin(一种具有异四恶嗪环的核黄素类似物)的抑制,但不受D-核糖(形成侧链连接)的抑制。核黄素中的异恶嗪环。为了进一步阐明转运系统的底物特异性,我们检查了几种具有类似于异恶嗪环的三环结构的药物对核黄素转运的影响。已发现氯噻嗪(一种吩噻嗪衍生物)在小肠和结肠中均抑制核黄素转运。还发现亚甲基蓝在两个位点都是有效的抑制剂。这些结果表明,某些三环型药物可能会干扰特定载体介导的转运系统对肠道核黄素的吸收。这些转运系统可能在三环型药物的吸收中发挥作用。

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