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Objective To explore the effect of galanin ( GAL) on locus coeruleus ( LC) neurons from neonatal rat and mechanism with its receptor GalR and potassium channel.Methods Brain slices from neonatal rats were prepared and the resting membrane potential and spontaneous action potential of LC neurons were recorded with whole cell patch-clamp configuration.GAL, AR-M1896 and potassium channel blockers were bath applied with different concentration.Results Bath application GAL induced hyperpolarization and inhibited firing rate of LC neurons.However, AR-M1896 ( a selective GalR2 agonist) did not induce significant effect on LC neurons, only at very high concentration(1μM) it induced slight hyperpolarization and reduced firing rate.The inhibitory effect of GAL was partially blocked by TEA ( an antagonist of voltage-dependent potassium channel) and significantly blocked by BaCl2(an antagonist of inward-rectifying potassium channels), while other potassium channels blockers such as Glybenclamide(ATP-sensitive potassium channel blocker),Charybdotoxin(large-conductance Ca2 +-activated K + channels blocker),Apamin(small-conductance Ca2 +-activated K +channels blocker) failed to block it.Conclusion GAL inhibits LC neurons from neonatal rats, mainly through GalR1.TEA-sensitive potassium channels and inward-rectifying potassium channels, but not ATP-sensitive potassium channel and calcium-activated potassium channel, are involved in this inhibition.
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Objective To study the protective effect of galanin on 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ)-induced oxidative stress and cell damage in HEK-293A cells and its possible mechanisms.Methods The expression of galanin and its three receptors (GalR1-3) in HEK-293A were determined with RTPCR technique.The cultured HEK-293A cells were divided into four groups:Control,DMNQ,DMNQ + GAL and DMNQ + AR-M1896 and the cell viability was measured with CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS).Results The RT-PCR data revealed the presence of galanin and its receptors in HEK-293A cells.The expression level was in the order of GalR2 =Galanin ＞ GalR3 ＞ GalR1.DMNQ caused oxidative stress and cell damage in HEK-293A cells with a dose-dependent manner with an IC50 =13.4 μM.Application of galanin reduced the DMNQ-induced cellular toxicity in HEK-293A,which increased cell viability by 24.4％ and 18.8％ in 1 μM and 100 nM,respectively.AR-M1896,an agonist of GalR2 had a similar effect,increased cell viability by 8.7％ and 8.9％ in 1 μM and 100 nM,respectively.Conclusion These data suggest that galanin has a protective effect on DMNQ-induced oxidative stress and cell damage in HEK-293A cells,probably mediated by GalR2.
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Galanin is a peptide with wide-ranging effects,especially within the central,peripheral nervous system and endocrine system.Many tumors of neuroendocrine origin,and also an increasing number of non-neuroendocrine cancers,have been shown to express galanin and/or its receptors.Expression of galanin peptide has been detected in pheochromocytoma,squamous cell carcinoma,pituitary adenoma,gastrointestinal cancers and so on.Galanin peptide plays an important role in tumori-genesis and progression of many kinds of tumors.Therefore,studying the roles of galanin and its receptors are helpful for diagnosis and treatment of tumors.