Pozzato G, Stebel M, Lunazzi G, Moretti M, Franzin F
Instituto di Patologia Medica, University School of Medicine, Trieste, Italy.
Scand J Clin Lab Invest. 1992 Nov;52(7):747-52. doi: 10.3109/00365519209115521.
The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism.
研究了西咪替丁、雷尼替丁和奥美拉唑对大鼠胃和肝乙醇脱氢酶（ADH）活性的影响。胃ADH发现两个明显的Km值（分别为220 mmol l-1和1043 mmol l-1），肝ADH有一个Km值（0.54 mmol l-1）。结果表明，西咪替丁对低Km值胃ADH产生非竞争性抑制作用，Ki为0.167 mmol l-1，对高Km值胃ADH产生竞争性抑制作用，Ki为2.3 mmol l-1。雷尼替丁仅对低Km值胃ADH呈现非竞争性抑制作用，Ki为12 mmol l-1。奥美拉唑仅影响低Km值胃ADH，Ki为5.6 mmol l-1，呈现线性混合型抑制。肝ADH仅被西咪替丁竞争性抑制，Ki为6.0 mmol l-1，而雷尼替丁和奥美拉唑均未观察到抑制作用。这些结果证实了西咪替丁对胃和肝ADH均有抑制作用；雷尼替丁和奥美拉唑对ADH活性及可能对首过代谢有轻微影响。
