Edamura K, Sasai H
Life Science Research Laboratory, Japan Tobacco Inc., Yokohama, Kanagawa.
Pharmacol Biochem Behav. 1998 Oct;61(2):175-9. doi: 10.1016/s0091-3057(98)00095-1.
It has been reported that 9-ethyladenine (9-EA) is an efficient inhibitor of APRT (adenine phosphoribosyltransferase) and that its administration causes self-injurious behavior (Lesch-Nyhan Syndrome-like symptoms) in HPRT (hypoxanthine-guanine phosphoribosyltransferase)-deficient mice. In contrast, we found neither any self-injurious behavior (SIB), such as visible injury or hair loss, nor any apparent decrease in APRT activity in HPRT-deficient mice treated with 9-EA. We also found that 9-EA has little irreversible or competitive inhibitory effect on APRT in vitro, even at a concentration of 10(-2) M. In light of the negative finding of SIB in APRT/HPRT double-deficient mice, it seems unlikely that SIB in HPRT-deficient mice is caused by lowered APRT activity. It is concluded that 9-EA is not a sufficient APRT inhibitor and cannot be used in experiments that mimic lowered APRT status in an animal model.
据报道，9-乙基腺嘌呤（9-EA）是腺嘌呤磷酸核糖转移酶（APRT）的有效抑制剂，给次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HPRT）缺陷小鼠施用9-EA会导致自伤行为（莱施-奈恩综合征样症状）。相比之下，我们在用9-EA处理的HPRT缺陷小鼠中既未发现任何自伤行为（SIB），如可见损伤或毛发脱落，也未发现APRT活性有任何明显降低。我们还发现，即使在浓度为10（-2）M时，9-EA在体外对APRT几乎没有不可逆或竞争性抑制作用。鉴于在APRT/HPRT双缺陷小鼠中未发现SIB这一阴性结果，HPRT缺陷小鼠中的SIB似乎不太可能是由APRT活性降低所致。结论是，9-EA不是一种有效的APRT抑制剂，不能用于模拟动物模型中APRT状态降低的实验。
