VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways
VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways
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DOI：
10.1111/bph.14051
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发表时间：
2017-12-01
影响因子：
7.3
通讯作者：
Sebastiao, Ana M.
中科院分区：
文献类型：
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作者：
Cunha-Reis, Diana;Ribeiro, Joaquim Alexandre;Sebastiao, Ana M.
血管活性肠肽（VIP）是海马突触传递的重要调节因子，通过激活VPAC（1）和VPAC（2）受体影响GABA能突触传递和海马神经元兴奋性。突触前GABA释放的增强与VIP对海马突触传递的调节有关。实验方法我们研究了VIP受体和偶联的转导通路参与了VIP对K+诱发的大鼠海马神经末梢[H-3]-GABA释放的增强作用。关键词VIP对[H-3]-GABA释放的增强作用在VPAC（1）受体拮抗剂PG 97- 269，但在VPAC（2）受体拮抗剂PG 99-465存在下转变为抑制，表明VPAC（1）受体的激活抑制GABA释放，而VPAC（2）受体的激活增强GABA释放。一种VPAC（1）受体激动剂通过激活蛋白质Gi/o抑制胞吐电压门控钙通道（VGCC）依赖性[H-3]-GABA释放，这种作用也依赖于PKC活性。VPAC（2）受体激动剂通过蛋白GS依赖性增强胞吐VGCC依赖性释放，结论VPAC（1）和VPAC（2）通过Gs蛋白依赖性和PKC依赖性机制介导[H-3]-GABA释放。VIP受体通过激活不同的信号转导通路对海马神经末梢释放GABA具有相反的作用。由于VPAC（1）和VPAC（2）受体位于阿蒙角的不同层，我们的研究结果表明，这些VIP受体对锥体细胞的突触传递具有不同的调节作用
BACKGROUND AND PURPOSEVasoactive intestinal peptide (VIP) is an important modulator of hippocampal synaptic transmission that influences both GABAergic synaptic transmission and glutamatergic cell excitability through activation of VPAC(1) and VPAC(2) receptors. Presynaptic enhancement of GABA release contributes to VIP modulation of hippocampal synaptic transmission.EXPERIMENTAL APPROACHWe investigated which VIP receptors and coupled transduction pathways were involved in VIP enhancement of K+-evoked [H-3]-GABA release from isolated nerve terminals of rat hippocampus.KEY RESULTSVIP enhancement of [H-3]-GABA release was potentiated in the presence of the VPAC(1) receptor antagonist PG 97-269 but converted into an inhibition in the presence of the VPAC(2) receptor antagonist PG 99-465, suggesting that activation of VPAC(1) receptors inhibits and activation of VPAC(2) receptors enhances, GABA release. A VPAC(1) receptor agonist inhibited exocytotic voltage-gated calcium channel (VGCC)-dependent [H-3]-GABA release through activation of protein Gi/o, an effect also dependent on PKC activity. A VPAC(2) receptor agonist enhanced both exocytotic VGCC-dependent release through protein Gs-dependent, PKA-dependent and PKC-dependent mechanisms and GABA transporter 1-mediated [H-3]-GABA release through a Gs protein-dependent and PKC-dependent mechanism.CONCLUSIONS AND IMPLICATIONSOur results show that VPAC(1) and VPAC(2) VIP receptors have opposing actions on GABA release from hippocampal nerve terminals through activation of different transduction pathways. As VPAC(1) and VPAC(2) receptors are located in different layers of Ammon's horn, our results suggest that these VIP receptors underlie different modulation of synaptic transmission to pyramidal cell