Melatonin receptor agonist ramelteon activates the extracellular signal-regulated kinase 1/2 in mouse cerebellar granule cells.

摘要: The melatonin receptors MT1 and MT2 take part in the regulation of activity (i.e. phosphorylation) extracellular-signal-regulated kinase (ERK1/2), an enzyme involved neuroplasticity. Primary cultures mouse rat cerebellar granule cells (CGC), which express both receptors, have been widely used as vitro model to study neuronal ERK1/2. A novel MT1/MT2 agonist, ramelteon, has recently become clinically available. In this study, we characterized its action on We CGC prepared from cerebella wild-type mice (MT1/MT2 CGC) MT1- MT2-knockout (KO) (MT1 KO CGC, respectively), employed a Western blot assay evaluate ERK1/2 phosphorylation. Ramelteon increased phosphorylation not only but also expressing one two receptors. stimulatory effect ramelteon was blocked by antagonist, 4P-PDOT, whereas luzindole. Pertussis toxin treatment did prevent activating pretreatment with tyrosine (Trk) inhibitor, K252a, did, suggesting that activation Trk may mediate melatonin-receptor dependent activation. conclusion, showed for first time is capable