Carenzi A, Guidotti A, Revuelta A, Costa E
J Pharmacol Exp Ther. 1975 Aug;194(2):311-8.
Analgesic doses of morphine and viminol R2 increase the turnover rate of dopamine (DA) in rat striatum but fail to increase the striatal concentration of adenosine 3',5'-monophosphate (cAMP) or the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor. When morphine is added to striatal homogenates, it changes neither the basal activity of adenylate cyclase nor the enzyme activation by DA. Similarly to morphine, haloperidol enhances the turnover rate of striatal DA, but unlike morphine it increases the affinity of TH for the pteridine cofactor and blocks the in vitro activation of striatal adenylacte cyclase by DA. Morphine (52 mumol/kg i.p.), viminol R2 (7 mumol/kg i.p.) or haloperidol (2.6 mumol/kg i.p.) fails to increase the striatal cAMP contrations. However (+)-amphetamine (4.8 mumol/kg i.p.) increases DA turnover rate and the striatal cAMP content, but, in doses up to 12.8 mumol/kg i.p., it fails to change the affinity of TH for the pteridine cofactor. This study shows that although (+)-amphetamine, haloperidol and morphine increase the turnover rate of striatal DA each drug possesses a specific profile in its action on molecular mechanisms that control the function of striatal dopaminergic synapses.
吗啡和维米诺R2的镇痛剂量可提高大鼠纹状体中多巴胺（DA）的周转率，但未能提高纹状体中3',5'-单磷酸腺苷（cAMP）的浓度，也未改变酪氨酸羟化酶（TH）对蝶啶辅因子的亲和力。当将吗啡添加到纹状体匀浆中时，它既不改变腺苷酸环化酶的基础活性，也不改变DA对该酶的激活作用。与吗啡相似，氟哌啶醇可提高纹状体DA的周转率，但与吗啡不同的是，它增加了TH对蝶啶辅因子的亲和力，并阻断了DA对纹状体腺苷酸环化酶的体外激活作用。吗啡（腹腔注射52 μmol/kg）、维米诺R2（腹腔注射7 μmol/kg）或氟哌啶醇（腹腔注射2.6 μmol/kg）均未能提高纹状体cAMP的浓度。然而，（+）-苯丙胺（腹腔注射4.8 μmol/kg）可提高DA周转率和纹状体cAMP含量，但在高达腹腔注射12.8 μmol/kg的剂量下，它未能改变TH对蝶啶辅因子的亲和力。这项研究表明，尽管（+）-苯丙胺、氟哌啶醇和吗啡均可提高纹状体DA的周转率，但每种药物在对控制纹状体多巴胺能突触功能的分子机制的作用方面都具有特定的特征。
