芳基乙酸代谢的研究。7. 不同剂量对豚鼠、小鼠和仓鼠体内2-萘乙酸结合模式的影响。

Studies on the metabolism of arylacetic acids. 7. The influence of varying dose size upon the conjugation pattern of 2-naphthylacetic acid in the guinea pig, mouse and hamster.

Emudianughe T S, Caldwell J, Smith R L

Department of Pharmacology, St Mary's Hospital Medical School, London, UK.

Xenobiotica. 1987 Jul;17(7):823-8. doi: 10.3109/00498258709043991.

Abstract

The influence of dose size upon the metabolic conjugation of 2-naphthylacetic acid with various amino acids and glucuronic acid has been studied in the guinea pig, mouse and hamster. 2. Guinea pigs conjugated 2-naphthylacetic acid with glycine and glucuronic acid. 3. Mice conjugated 2-naphthylacetic acid with glycine, taurine and glucuronic acid. Taurine conjugation had the highest capacity, and both this and the glycine mechanism were saturated at doses above 100 mg/kg. 4. Hamsters utilized glutamine, glycine, taurine and glucuronic acid for the conjugation of 2-naphthylacetic acid. No conjugation pathway was saturated by doses up to 200 mg/kg. 5. The thus-far unique ability of 2-naphthylacetic acid to evoke multiple amino acid conjugations, using the taurine and glutamine mechanisms hitherto unknown in these species, appears to be due to its affinity for previously unrecognized enzyme systems, rather than to saturation of 'normal' pathways revealing novel routes at high doses.

摘要

已在豚鼠、小鼠和仓鼠中研究了剂量大小对2-萘乙酸与各种氨基酸及葡萄糖醛酸代谢结合的影响。2. 豚鼠使2-萘乙酸与甘氨酸和葡萄糖醛酸结合。3. 小鼠使2-萘乙酸与甘氨酸、牛磺酸和葡萄糖醛酸结合。牛磺酸结合能力最强，在剂量高于100 mg/kg时，这种结合以及甘氨酸结合机制均达到饱和。4. 仓鼠利用谷氨酰胺、甘氨酸、牛磺酸和葡萄糖醛酸对2-萘乙酸进行结合。在剂量高达200 mg/kg时，没有结合途径达到饱和。5. 2-萘乙酸具有一种迄今独特的能力，即利用这些物种中迄今未知的牛磺酸和谷氨酰胺机制引发多种氨基酸结合，这似乎是由于它对以前未被识别的酶系统具有亲和力，而不是由于“正常”途径在高剂量下饱和从而揭示出新的途径。