Activation of neuromedin U type 1 receptor inhibits L-type Ca2+ channel currents via phosphatidylinositol 3-kinase-dependent protein kinase C epsilon pathway in mouse hippocampal neurons

摘要: Abstract Neuromedin U (NMU) plays very important roles in the central nervous system. However, to date, any role of NMU hippocampal neurons and relevant mechanisms still remain unknown. In present study, we report that selectively inhibits L-type high-voltage-gated Ca2+ channels (HVGCC) mouse neurons, which type 1 receptor (NMUR1), but not NMUR2, is endogenously expressed. wild mice, (0.1 μM) reversibly inhibited HVGCC barium currents (IBa) by ∼ 28%, while NMUR1−/− mice had no significant effects. Intracellular infusion GDP-β-S or a selective antibody raised against Goα, as well pretreatment with pertussis toxin, blocked inhibitory effects NMU, indicating involvement Go-protein. This NMUR1-mediated effect did display characteristics direct interaction between G-protein βγ subunit (Gβγ) HVGCC, was abolished dialyzing cells QEHA peptide an Gβ. The classical novel protein kinase C (PKC) antagonist calphostin C, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, responses, whereas PKC Go6976 such Cells dialyzed epsilon isoform (PKCe) specific peptide, GAVSLLPT, responses. contrast, inactive PKCe control scramble LSGTLPAV, were observed. summary, these results suggest via activation NMUR1 downstream Gβγ, PI3K, signaling pathway.