止泻药洛哌丁胺对血栓素A(2)诱导大鼠离体结肠Cl(-)分泌的抑制作用。
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铃木T，酒井H，伊光A，竹口N
止泻药洛哌丁胺对血栓素A(2)诱导大鼠离体结肠Cl(-)分泌的抑制作用。
中华药物学杂志2000 10月;295(1):233-8。
- PubMed ID
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10991984 (PubMed视图］
- 摘要
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抗肿瘤药物伊立替康在临床上会引起严重的腹泻。血栓素A(2) (TXA(2))是伊立替康释放的一种新型刺激大鼠结肠Cl(-)分泌的生理物质。本文研究了抗腹泻药洛哌丁胺对伊立替康诱导的Cl(-)分泌的影响;9,11 -上皮-11,12-甲烷-血栓烷A(2) (STA(2))，稳定的TXA(2)模拟物;和前列腺素E(2) (PGE(2))。在阿托品存在的情况下，洛哌丁胺以浓度依赖的方式抑制伊立替康、STA(2)和PGE(2)诱导的Cl(-)分泌。然而，该药更有效地抑制伊立替康和STA(2)诱导的分泌(IC(50) = 0。与PGE(2)诱导的分泌(IC(50) = 23 microM)相比，分别为7和1.2 microM。阿片剂拮抗剂纳洛酮不影响洛哌丁胺的抗分泌作用。与洛哌丁胺的情况类似，W-7，一种特异性钙调素拮抗剂，更有效地抑制STA(2)诱导的Cl(-)分泌(IC(50) = 5 microM)，而PGE(2)诱导的Cl(-)分泌(IC(50) = 36 microM)。 W-5, a low-affinity calmodulin antagonist (a dechlorinated control analog of W-7), also inhibited the STA(2)-induced secretion, but this effect was much less than that of W-7. STA(2)-induced increase in the intracellular free Ca(2+) concentration of single colonic crypt cells was not affected by loperamide. We suggest that loperamide efficiently inhibits the TXA(2)-induced secretion by blocking the calmodulin system in the colonic epithelium. The present results may explain why coadministration of loperamide with irinotecan is clinically efficient for avoiding the irinotecan-induced side effect of diarrhea.