血红素生物合成中间体在离体肠制剂中的药理作用。

Pharmacological effects of haem biosynthetic intermediates in isolated intestinal preparations.

作者信息

Cutler M G, Arrol S

出版信息

Eur J Pharmacol. 1987 Feb 24;134(3):249-56. doi: 10.1016/0014-2999(87)90355-4.

Abstract

Spontaneous contractile activity of isolated rabbit jejunal preparations bathed in oxygenated Ringer-Locke buffered to pH 7.0 was inhibited by haemin and by all haem biosynthetic intermediates tested, there being decreases in tone or amplitude of contractions. Effects were concentration-dependent. The minimal effective concentrations were 0.4 mM for porphobilinogen, 0.6 mM for protoporphyrin IX, 0.8 mM for haemin, 3.0 mM for delta-aminolaevulinic acid (ALA), 4.5 mM for coproporphyrin I, 3.0 mM for glycine and 6.0 mM for succinate. Inhibition was short-lasting, other than for protoporphyrin (2.3 mM) and haemin (3.0 mM). Leucine at concentrations up to 12 mM had no significant effect. Inhibitory effects of ALA were followed by contractions of increased amplitude; pretreatment of preparations with indomethacin (56 microM) prevented this enhancement of contractile activity. Tone in isolated preparations of human taenia coli bathed in oxygenated Ringer-Locke was decreased by ALA (1.5-6.0 mM). A significant increase of tone followed the initial inhibitory effect. The relevance of these findings to acute porphyria is discussed.

摘要

在pH 7.0的充氧林格 - 洛克缓冲液中孵育的离体兔空肠制剂的自发收缩活动受到血红素和所有测试的血红素生物合成中间体的抑制，收缩张力或幅度降低。作用呈浓度依赖性。最小有效浓度分别为：胆色素原0.4 mM、原卟啉IX 0.6 mM、血红素0.8 mM、δ-氨基-γ-酮戊酸（ALA）3.0 mM、粪卟啉I 4.5 mM、甘氨酸3.0 mM和琥珀酸6.0 mM。除了原卟啉（2.3 mM）和血红素（3.0 mM）外，抑制作用持续时间较短。浓度高达12 mM的亮氨酸无显著影响。ALA的抑制作用后是收缩幅度增加；用吲哚美辛（56 microM）预处理制剂可防止这种收缩活动增强。在充氧林格 - 洛克液中孵育的人结肠带绦虫离体制剂的张力被ALA（1.5 - 6.0 mM）降低。在最初的抑制作用后张力显著增加。讨论了这些发现与急性卟啉症的相关性。