Chawla A, Karl P I, Reich R N, Narasimhan G, Michaud G A, Fisher S E, Schneider B L
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY, USA.
Dig Dis Sci. 1995 May;40(5):943-8. doi: 10.1007/BF02064181.
Olsalazine (OLZ), a relatively new form of 5-aminosalicylic acid (5-ASA), is being used for the treatment of colitis. A major side effect of olsalazine is diarrhea, reported in 12-25% of patients. One suggested mechanism for this side effect is enhanced ileal water and electrolyte secretion. We propose that OLZ may also inhibit ileal bile acid (BA) transport, resulting in choleretic diarrhea. This would result in excess BAs reaching the colon, with consequent BA-induced secretory diarrhea. Therefore, we studied the effect of OLZ on rat ileal absorption of taurocholate. BA uptake was determined in rat ileal segments, everted sacs, brush border membrane vesicles (BBMV), and Xenopus laevis oocytes. Segments and everted sacs were treated with 5 mM OLZ for 30 min prior to and throughout 10-min taurocholate (Tc) uptake. Terminal ileal BBMV were used to study the effect of OLZ on sodium-dependent bile acid uptake independent of cellular metabolism. Direct effects on the bile acid carrier were examined using Xenopus laevis oocytes expressing the cloned apical rat ileal BA transporter. In ileal segments 5 mM OLZ inhibited 10-min Tc uptake by 69.4 +/- 8.8% (P < 0.01) (N = 10 animals). Increasing concentrations of OLZ resulted in a dose-dependent inhibition of Tc uptake. Ten-minute Tc uptake with 0.5, 1.0, 2.0, 2.5, and 5 mM OLZ was inhibited by 13.5, 39.6, 49.7, and 70.5%, respectively. In BBMV, OLZ inhibited 45-sec Tc uptake in a dose-dependent manner but did not effect Na-dependent L-alanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
奥沙拉嗪（OLZ）是5-氨基水杨酸（5-ASA）的一种相对较新的形式，正用于治疗结肠炎。奥沙拉嗪的一个主要副作用是腹泻，12%至25%的患者有此报告。这种副作用的一种推测机制是回肠水和电解质分泌增强。我们提出OLZ可能还会抑制回肠胆汁酸（BA）转运，从而导致胆汁性腹泻。这将导致过量的胆汁酸到达结肠，进而引起胆汁酸诱导的分泌性腹泻。因此，我们研究了OLZ对大鼠回肠牛磺胆酸盐吸收的影响。在大鼠回肠段、外翻囊、刷状缘膜囊泡（BBMV）和非洲爪蟾卵母细胞中测定胆汁酸摄取。在10分钟牛磺胆酸盐（Tc）摄取之前及整个过程中，将回肠段和外翻囊用5 mM OLZ处理30分钟。使用末端回肠BBMV研究OLZ对不依赖细胞代谢的钠依赖性胆汁酸摄取的影响。使用表达克隆的大鼠回肠顶端胆汁酸转运体的非洲爪蟾卵母细胞检查对胆汁酸载体的直接作用。在回肠段，5 mM OLZ使10分钟Tc摄取抑制了69.4±8.8%（P<0.01）（N = 10只动物）。OLZ浓度增加导致Tc摄取呈剂量依赖性抑制。0.5、1.0、2.0、2.5和5 mM OLZ的10分钟Tc摄取分别被抑制了13.5%、39.6%、49.7%和70.5%。在BBMV中，OLZ以剂量依赖性方式抑制45秒Tc摄取，但不影响钠依赖性L-丙氨酸摄取。（摘要截短于250字）
