Delbende C, Jégou S, Tranchand-Bunel D, Pelletier G, Vaudry H
Groupe de Recherche en Endocrinologie Moléculaire, UA CNRS 650, Faculté des Sciences, Université de Rouen, Mont-Saint-Aignan, France.
Brain Res. 1987 Oct 13;423(1-2):203-12. doi: 10.1016/0006-8993(87)90841-9.
A possible dopaminergic regulation of hypothalamic proopiomelanocortin (POMC)-containing neurons has been investigated in rats by means of in vivo and in vitro approaches. Acute or 3-weeks chronic in vivo treatments with the dopaminergic agonists apomorphine (1 mg/kg: s.c.) and 2-Br-alpha-ergocriptine (2.5 mg/kg; s.c.) or the dopaminergic antagonist haloperidol (0.15-3 mg/kg; i.p.) had no significant effect on the concentration of alpha-melanocyte-stimulating hormone (alpha-MSH) in two hypothalamic regions: arcuate nucleus (AN) and dorsolateral area (DLH). In the same way, chronic administration of the dopaminergic agonists or antagonist did not induce any change in hypothalamic contents of beta-endorphin, another peptide derived from POMC. Reverse-phase high-performance liquid chromatographic analysis revealed that acetic acid extracts of AN and DLH both contained two major forms of alpha-MSH-like peptides: deacetylated alpha-MSH and authentic alpha-MSH. The ratio between these two forms was not altered after acute haloperidol treatment (3 mg/kg, i.p.). The possible effect of dopamine on the release of hypothalamic alpha-MSH was studied in vitro using perifused rat hypothalamic slices. Infusion of dopamine (10(-7)-10(-5)M) or its antagonist haloperidol (10(-5)M) had no effect on spontaneous alpha-MSH release from hypothalamic tissue. In addition, none of these drugs had any effect on potassium (50 mM)-induced alpha-MSH release. It is concluded that dopaminergic neurons are not involved in the regulation of synthesis, post-translational processing (acetylation) or release of hypothalamic alpha-MSH.
通过体内和体外实验方法，研究了大鼠下丘脑含阿片促黑素皮质激素原（POMC）神经元可能存在的多巴胺能调节机制。分别用多巴胺能激动剂阿扑吗啡（1毫克/千克，皮下注射）、2-溴-α-麦角隐亭（2.5毫克/千克，皮下注射）或多巴胺能拮抗剂氟哌啶醇（0.15 - 3毫克/千克，腹腔注射）进行急性或为期3周的慢性体内给药，对下丘脑两个区域：弓状核（AN）和背外侧区（DLH）中的α-黑素细胞刺激素（α-MSH）浓度均无显著影响。同样，长期给予多巴胺能激动剂或拮抗剂也未引起下丘脑β-内啡肽含量的任何变化，β-内啡肽是另一种源自POMC的肽。反相高效液相色谱分析显示，AN和DLH的乙酸提取物均含有两种主要形式的α-MSH样肽：脱乙酰化α-MSH和天然α-MSH。急性氟哌啶醇处理（3毫克/千克，腹腔注射）后，这两种形式之间的比例未发生改变。使用灌流的大鼠下丘脑切片在体外研究了多巴胺对下丘脑α-MSH释放的可能影响。灌注多巴胺（10^(-7)-10^(-5)M）或其拮抗剂氟哌啶醇（10^(-5)M）对下丘脑组织中α-MSH的自发释放没有影响。此外，这些药物均对钾（50 mM）诱导的α-MSH释放没有任何作用。结论是，多巴胺能神经元不参与下丘脑α-MSH合成、翻译后加工（乙酰化）或释放的调节。
