Dzirkale Zane, Rumaks Juris, Svirskis Simons, Mazina Olga, Allikalt Anni, Rinken Ago, Jekabsons Kaspars, Muceniece Ruta, Klusa Vija
Department of Pharmacology, Faculty of Medicine, University of Latvia, 1A Sarlotes St, Riga, LV-1001, Latvia.
Behav Brain Res. 2013 Nov 1;256:5-9. doi: 10.1016/j.bbr.2013.08.002. Epub 2013 Aug 8.
The present study for the first time is devoted to identify central effects of synthetic lunasin, a 43 amino acid peptide. A markedly expressed neuroleptic/cataleptic effect was observed at low (0.1-10 nmol/mouse) centrally administered doses in male C57Bl/6 mice. Lunasin considerably reduced the amphetamine hyperlocomotion but weakly apomorphine climbing behaviour. No influence on ketamine and bicuculline effects was observed. Binding assay studies demonstrated modest affinity of lunasin for the dopamine D₁ receptor (Ki=60 ± 15 μM). In a functional assay of cAMP accumulation on live cells lunasin antagonised apomorphine effect on D₁ receptor activation (pEC₅₀=6.1 ± 0.3), but had no effect in cells expressing D₂ receptors. The obtained data suggest that lunasin's action at least in part is provided via dopaminergic D1 receptor pathways. However, other non-identified mechanisms (probably intracellular) may play an important role in lunasin's central action. Nevertheless further studies of lunasin are promising, particularly taking into account a necessity for novel type of antipsychotic drugs.
本研究首次致力于确定合成的月桂酰胺（一种43个氨基酸的肽）的中枢效应。在雄性C57Bl/6小鼠中，经中枢给药低剂量（0.1 - 10 nmol/小鼠）时观察到明显的抗精神病/僵住效应。月桂酰胺显著降低了苯丙胺引起的运动亢进，但对阿扑吗啡诱导的攀爬行为影响较弱。未观察到对氯胺酮和荷包牡丹碱效应的影响。结合试验研究表明月桂酰胺对多巴胺D₁受体具有适度亲和力（Ki = 60 ± 15 μM）。在活细胞上进行的cAMP积累功能试验中，月桂酰胺拮抗了阿扑吗啡对D₁受体激活的作用（pEC₅₀ = 6.1 ± 0.3），但对表达D₂受体的细胞无影响。所获得的数据表明，月桂酰胺的作用至少部分是通过多巴胺能D1受体途径实现的。然而，其他未明确的机制（可能是细胞内机制）可能在月桂酰胺的中枢作用中发挥重要作用。尽管如此，月桂酰胺的进一步研究前景广阔，特别是考虑到新型抗精神病药物的必要性。
