Chou J, Tang J, Yang H Y, Costa E
J Pharmacol Exp Ther. 1984 Apr;229(1):171-4.
In rats, daily doses of haloperidol repeated for various time periods increase striatal Met5-enkephalin-Arg6-Phe7 (YGGFMRF) immunoreactivity in a time- and dose-dependent manner. This increase occurred also in other dopamine-rich brain areas. After intraventricular captopril (0.5 mg), the accumulation rate of immunoreactive YGGFMRF was greater in haloperidol- than in saline-injected rats. Intraventricular captopril inhibits the YGGFMRF degradation; hence the greater accumulation rate of YGGFMRF caused by captopril in haloperidol-treated rats suggests that this drug increases the YGGFMRF biosynthesis. A slower rate of YGGFMRF release in haloperidol-treated rats can be excluded as a cause for the drug-induced increase in striatal content of this peptide because the release rates of YGGFMRF elicited by K+ were similar in striatal slices of haloperidol- and saline-treated rats. The similarities between the accumulation rate of immunoreactive YGGFMRF and of Met5-enkephalin induced by haloperidol suggest that haloperidol increases the biosynthesis of the specific messenger RNA for preproenkephalin, an opioid peptide precursor, which contains one copy of YGGFMRF and several copies of Met5-enkephalin.
在大鼠中，不同时间段每日重复给予氟哌啶醇，可使纹状体中Met5-脑啡肽-精氨酸6-苯丙氨酸7（YGGFMRF）免疫反应性呈时间和剂量依赖性增加。这种增加在其他富含多巴胺的脑区也有发生。脑室内注射卡托普利（0.5毫克）后，免疫反应性YGGFMRF在氟哌啶醇注射大鼠中的积累速率高于生理盐水注射大鼠。脑室内注射卡托普利可抑制YGGFMRF的降解；因此，卡托普利在氟哌啶醇治疗大鼠中导致的YGGFMRF积累速率更高，表明该药物增加了YGGFMRF的生物合成。氟哌啶醇治疗大鼠中YGGFMRF释放速率较慢，可排除其作为药物诱导该肽纹状体含量增加的原因，因为在氟哌啶醇和生理盐水治疗大鼠的纹状体切片中，K⁺引发的YGGFMRF释放速率相似。氟哌啶醇诱导的免疫反应性YGGFMRF和Met5-脑啡肽积累速率之间的相似性表明，氟哌啶醇增加了前脑啡肽原（一种阿片肽前体）特异性信使核糖核酸的生物合成，前脑啡肽原包含一个YGGFMRF拷贝和几个Met5-脑啡肽拷贝。
