Fredholm B B
Med Biol. 1977 Feb;55(1):61-5.
The possible involvement of cyclic nucleotide phosphodiesterase (PDE) in the supersensitivity to dopamine-receptor agonists after chronic treatment with neuroleptic drugs has been studied. Rats were given haloperidol in the drinking water for 18 days and finally injected i.p. with 10 mg/kg haloperidol. During and after this treatment the low Km form of the cyclic AMP PDE in a 10,000 g supernatant of the striata was reduced. The loss in enzyme activity was associated with a change in the chromatographic behaviour on DEAE-cellulose. The difference between control- and haloperidol-treated rats was most pronounced in the presence of 1 mM ethylene glycol-bis(aminoethylether)tetraacetic acid (EGTA) and was essentially abolished at 1 mM Ca++. This decrease in cyclic AMP PDE may explain some of the supersensitivity to dopamine-receptor agonists observed following chronic neuroleptic treatment.
已经研究了环核苷酸磷酸二酯酶（PDE）在使用抗精神病药物进行长期治疗后对多巴胺受体激动剂超敏反应中可能的作用。给大鼠在饮用水中加入氟哌啶醇，持续18天，最后腹腔注射10mg/kg氟哌啶醇。在该治疗期间及之后，纹状体10,000g上清液中环磷酸腺苷PDE的低Km形式减少。酶活性的丧失与在DEAE-纤维素上的色谱行为变化有关。在存在1mM乙二醇双（氨基乙基醚）四乙酸（EGTA）的情况下，对照大鼠和氟哌啶醇处理大鼠之间的差异最为明显，而在1mM Ca++时基本消除。环磷酸腺苷PDE的这种降低可能解释了在长期抗精神病药物治疗后观察到的对多巴胺受体激动剂的一些超敏反应。
