Apomorphine enantiomers' effects on dopamine metabolism: receptor and non-receptor related actions.
Apomorphine enantiomers' effects on dopamine metabolism: receptor and non-receptor related actions.
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阿朴吗啡对映体对多巴胺代谢的影响：受体和非受体相关作用。
DOI：
10.1016/0014-2999(86)90489-9
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发表时间：
1986
影响因子：
5
通讯作者：
A. Salama
中科院分区：
文献类型：
--
作者：
C. Saller;A. Salama
阿朴吗啡对映体可抑制大鼠纹状体突触体内多巴胺的合成，R(−)-APO的抑制作用约为S(+)-APO的两倍。DA受体拮抗剂舒必利可部分拮抗(−)-APO的抑制作用，提示(−)-APO而不是(+)-APO对多巴胺合成的抑制作用可能至少部分是由受体介导的。加入酪氨酸羟基酶的人工辅因子6-甲基-5，6，7，8-四氢生物蝶呤(6-MPH4)可部分拮抗两种对映体的抑制作用，对(+)对映体的抑制作用明显增强。这些数据表明，APO对映体可能直接抑制突触体内调节多巴胺合成的酶。此外，对预先与(−)-APO孵育，然后清洗以去除(−)-APO的突触体中DA合成速率的研究表明，(−)-APO可能被突触体保留。初步研究还表明，突触体可以蓄积[~3H](−)-APO。虽然两种APO对映体在体外都能抑制DA的合成，但只有(−)-APO在体内降低了纹状体DA代谢产物的浓度，这种减少可被DA受体拮抗剂氟哌啶醇所阻止。此外，6-MPH4可抑制(−)-APO产生的DA代谢物3，4-二羟基苯乙酸的减少，但不能阻止DA代谢物高香草酸的减少。
The enantiomers of apomorphine (APO) inhibited dopamine synthesis in rat striatal synaptosomes, with R(−)-APO being about twice as potent as S(+)-APO. Sulpiride, a DA receptor antagonist, partially antagonized the inhibitory effects of only (−)-APO, suggesting that (−)-APO's, but not (+)-APO's effects on dopamine synthesis may be at least partially receptor-mediated. The addition of 6-methyl-5,6,7,8-tetrahydrobiopterine (6-MPH4), an artificial cofactor for tyrosine hydroxylase, partially antagonized the inhibitory effects of both enantiomers, being considerably more effective against the (+)enantiomer. These data suggest that the APO enantiomers may directly inhibit enzymes within the synaptosome which regulate dopamine synthesis. Furthermore, investigations measuring DA synthesis rates in synaptosomes that had been pre-incubated with (−)-APO and then washed to remove the (−)-APO in the medium, indicate that (−)-APO may be retained by synaptosomes. Preliminary studies measuring the accumulation of [3H](−)-APO by synaptosomes also suggest that synaptosomes can accumulate APO. Although both APO enantiomers suppressed DA synthesis in vitro, only (−)-APO reduced striatal DA metabolite concentrations in vivo, and this reduction was prevented by haloperidol, a DA receptor antagonist. In addition, 6-MPH4prevented the decrease in the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) produced by (−)-APO but not the decrease in the DA metabolite homovanillic acid (HVA).
儿茶酚胺和相关化合物对二氢蝶啶还原酶的抑制作用。
DOI：
10.1016/0167-4838(83)90426-0
发表时间：
1983
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Shen,RS
通讯作者：
Shen,RS