Lunasin-induced behavioural effects in mice: focus on the dopaminergic system.
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.
Department of Pharmacology, Faculty of Medicine, University of Latvia, 1A Sarlotes St, Riga, LV-1001, Latvia.
Zane
Z
Dzirkale
Juris
J
Rumaks
Simons
S
Svirskis
Olga
O
Mazina
Anni
A
Allikalt
Ago
A
Rinken
Kaspars
K
Jekabsons
Ruta
R
Muceniece
Vija
V
Klusa
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001640:Bicuculline / Q000009:adverse effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D002491:Central Nervous System Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D030262:Soybean Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D002491:Central Nervous System Agents; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; C120514:GM2S-1 protein, soybean; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D030262:Soybean Proteins; D007649:Ketamine; D000661:Amphetamine; D000242:Cyclic AMP; D001058:Apomorphine; D001640:Bicuculline
Behaviour; Dopamine receptors; Lunasin; cAMP