Effects of isomers of hydroxyaporphines on dopamine metabolism in rat brain regions.
Effects of isomers of hydroxyaporphines on dopamine metabolism in rat brain regions.
复制标题
羟基阿朴啡异构体对大鼠脑区多巴胺代谢的影响。
DOI：
10.1016/0006-2952(90)90538-v
复制
发表时间：
1990
影响因子：
5.8
通讯作者：
Neumeyer,JL
中科院分区：
文献类型：
--
作者：
Baldessarini,RJ;Marsh,ER;Kula,NS;Zong,RS;Gao,YG;Neumeyer,JL
采用三种方法研究了二羟基阿啡和单羟基阿啡同分异构体对大鼠脑椎体外（纹状体）和边缘（伏隔核）多巴胺代谢的影响：(1)高香草酸（HVA）与DA之比的变化；(2)在“开环”条件下抑制多巴（DOPA）脱羧为DA后的积累；(3)γ-丁内酯（GBL）预处理后对突触前DA自受体提供选择性作用。在所有模型中，阿波啡（APO）、n- n-丙基去阿波啡（NPA）和11-羟基-n- n- n-丙基去阿波啡（11-OH-NPa）的DA激动剂r（−）异构体在两个脑区均表现出一致的剂量依赖性抑制；正如预期的那样，抗精神病药氟哌啶醇仅在前两种模型中具有相反的作用。NPA和11-OH-NPa的S（+）异构体已显示出抗多巴胺能活性的行为证据，特别是在边缘系统。与神经抑制剂不同，5(+)NPA在伏隔核或纹状体组织中没有表现出增强DA合成的作用，相反，在所有三个测试范式中，5(+)NPA像其sr（−）对映体一样抑制DA合成。单独给药S(+)11-OH-NPa对HVA/DA比的影响较小，对（−）11-OH-NPa没有拮抗作用，在第二种模型中微弱地增加了DOPA的积累，在第三种模型中没有作用——都没有区域选择性。在自身受体功能测试中，二羟基阿啡S(+)NPA抑制DA合成，而非ts (+)11-OH-NPa，而这种作用在很大程度上被氟哌啶醇逆转，三er（−）阿啡的抑制作用也是如此。然而，在这个模型中，thers (+)NPA和ors (+)11-OH-NPa都没有像氟哌啶醇那样拮抗r(−)APO的da合成抑制作用。总的来说，这些结果与r(−)NPA和11-OH-NPa在大鼠脑D-2受体位点具有高亲和力并表现出典型DA激动剂的行为效应的证据一致。NPA对DA合成的非立体选择性抑制作用可能反映了其作为一种内在活性非常低的弱DA激动剂的活性，但也可能包括对酪氨酸羟化酶的直接“儿茶酚效应”。相反，R(−)11-OH-NPa似乎是一种立体选择性的D-2激动剂，对自身受体和突触后受体都有活性，对其儿茶酚-阿啡同源物的DA代谢缺乏非立体特异性作用。这可能是进一步表征多巴胺受体和自受体的有用探针。
The effects of isomers of di- and monohydroxyaporphines on cerebral dopamine (DA) metabolism were evaluated in representative extrapyramidal (corpus striatum) and limbic (nucleus accumbens septi) tissues of rat brain by three methods: (1) changes in the ratio of homovanillic acid (HVA) to DA, (2) accumulation ofl-dihydroxyphenylalanine (DOPA) after inhibiting its decarboxylation to DA under “open-loop” conditions, as well as (3) after γ-butyrolactone (GBL) pretreatment to provide selective effects at presynaptic DA autoreceptors. The DA-agonistR(−) isomers of the aporphines apomorphine (APO),N-n-propylnorapomorphine (NPA), and 11-hydroxy-N-n-propyl-noraporphine (11-OH-NPa) showed consistent dose-dependent inhibition of DA synthesis in both brain regions with all models; the neuroleptic haloperidol had the opposite effect in the first two models only, as expected. The S(+) isomers of NPA and 11-OH-NPa have shown behavioral evidence of antidopaminergic activity, especially in the limbic system. Unlike the neuroleptic, 5(+)NPA did not show DA-synthesis enhancing actions in accumbens or striatal tissue but, instead, inhibited DA synthesis like itsR(−) antipode in all three test paradigms.S(+)11-OH-NPa given alone produced minor changes in the HVA/DA ratio and did not antagonizeR(−)11-OH-NPa, weakly increased accumulation of DOPA in the second model, and had no effect in the third—all without regional selectivity. In the test of autoreceptor functioning, the dihydroxyaporphine S(+)NPA, but notS(+)11-OH-NPa, inhibited DA synthesis and this effect, in turn, was largely reversed by haloperidol, as were the inhibitory effects of the threeR(−)aporphines tested. In this model, however, neitherS(+)NPA norS(+)11-OH-NPa antagonized the DA-synthesis inhibiting effect ofR(−)APO as haloperidol did. Overall, these results are consistent with evidence thatR(−)NPA and 11-OH-NPa have high affinity at D-2 receptor sites in rat brain and show behavioral effects of typical DA agonists. The non-stereoselective inhibitory effects of NPA on DA synthesis may reflect its activity as a weak DA agonist with very low intrinsic activity, but may also include a direct “catechol-effect” on tyrosine hydroxylase. In contrast,R(−)11-OH-NPa appears to be a stereoselective D-2 agonist, active at autoreceptors as well as postsynaptic receptors, that lacks the nonstereospecific effects on DA metabolism of its catechol-aporphine congener. It may be a useful probe for the further characterization of dopamine receptors and autoreceptors.
登录
查看更多内容
新型多巴胺受体激动剂和拮抗剂，对自身受体具有优先作用。
影响因子：
7.3
作者：
A. Johansson;L. Arvidsson;U. Hacksell;J. Nilsson;K. Svensson;S. Hjorth;D. Clark;A. Carlsson;D. Sanchez;B. Andersson
通讯作者：
B. Andersson
溴隐亭可拮抗可卡因对大鼠的行为影响。
DOI：
10.1016/0893-133x(89)90024-9
发表时间：
1989
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Campbell,A;Baldessarini,RJ;Cremens,C;Teicher,MH;Marsh,E;Kula,NS
通讯作者：
Kula,NS
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。
影响因子：
5
作者：
C. Saller;A. Salama
通讯作者：
A. Salama
合成镇痛药和其他苯基哌啶：对多巴胺和其他单胺小鼠前脑组织的吸收和储存的影响。
影响因子：
6.1
作者：
Baldessarini,RJ;Kula,NS;Francoeur,D;Finklestein,SP;Murphy,F;Neumeyer,JL
通讯作者：
Neumeyer,JL
多巴胺能激动剂和拮抗剂活性的立体化学和构象模型：进一步评估。
影响因子：
3.8
作者：
Froimowitz,M;Baldessarini,RJ
通讯作者：
Baldessarini,RJ