Tomei S, Yuasa H, Inoue K, Watanabe J
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Drug Deliv. 2001 Jul-Aug;8(3):119-24. doi: 10.1080/107175401316906874.
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.
本研究旨在从动力学角度表征大鼠结肠中新发现的载体介导的核黄素转运系统，将其与小肠中的该系统进行比较，并探究这些转运系统在肠道药物吸收中的潜在作用。通过测量外翻肠组织囊泡的初始摄取量来评估核黄素转运，结果表明结肠中的核黄素转运具有饱和性，米氏常数（Km）为0.13微摩尔，最大转运速率（Jmax）为0.74皮摩尔/分钟/100毫克湿组织重量（wtw）。结肠中的Km和Jmax均小于小肠中的（分别为0.57微摩尔和4.26皮摩尔/分钟/100毫克wtw），这表明结肠中的转运系统对底物的亲和力更高，但其转运能力小于小肠中的对应系统。与小肠类似，结肠中载体介导的核黄素转运依赖于钠离子，且受到核黄素类似物硫色素（一种具有异咯嗪环的核黄素类似物）的抑制，但不受D - 核糖的抑制，D - 核糖是构成核黄素中与异咯嗪环相连的侧链。为了进一步阐明转运系统的底物特异性，我们研究了几种具有与异咯嗪环相似三环结构的药物对核黄素转运的影响。发现吩噻嗪衍生物氯丙嗪可抑制小肠和结肠中的核黄素转运。亚甲蓝在这两个部位也被发现是一种有效的抑制剂。这些结果表明，一些三环类药物可能通过特定的载体介导转运系统干扰肠道核黄素的吸收。这些转运系统可能在三环类药物的吸收中发挥作用。
