Adenosine A2 receptors modulate hippocampal synaptic transmission via a cyclic-AMP-dependent pathway.
Adenosine A2 receptors modulate hippocampal synaptic transmission via a cyclic-AMP-dependent pathway.
复制标题
腺苷 A2 受体通过环 AMP 依赖性途径调节海马突触传递。
DOI：
10.1016/s0306-4522(97)00504-6
复制
发表时间：
1998
期刊：
影响因子：
3.3
通讯作者：
Mogul,DJ
中科院分区：
文献类型：
--
作者：
Kessey,K;Mogul,DJ
腺苷A2受体的阻断已显示出显著降低大鼠海马CA 1区中破伤风诱导的长时程增强的水平[Kessey K.等人（1997）Brain Res.756，184-190; Sekino Y.等人（1991）Biochem.biophys.通信资源181，1010-1014]。在本研究中，A2受体的激活和阻断的调制正常的突触传递和破伤风诱导的长时程增强的影响进行了检查在大鼠海马脑片的Schaffer-CA 1突触。通过树突状场兴奋性突触后电位测量，A2受体激活可逆地增强低频测试脉冲诱发的突触传递。在A1受体阻断的情况下，A2激活进一步增强兴奋性突触后电位，而A2受体阻断导致兴奋性突触后电位可逆性降低。A2 a受体激动剂CGS 21680对兴奋性突触后电位无影响，表明在正常生理条件下，A2 b受体的紧张性激活有助于突触传递。此外，我们还研究了A2受体对破伤风诱导的长时程增强的作用。在对照条件下，单次破伤风增强兴奋性突触后电位的63.5%，相对于基线破伤风后30分钟。相比之下，在A2阻断期间，破伤风诱导的长时程增强为21.3%。A2受体激活可使破伤风诱导的长时程增强水平增加至90.2%。因为已知A2受体刺激环AMP积累，所以检查了环AMP的可能参与。直接腺苷酸环化酶激活剂毛喉素和环腺苷酸的膜渗透性类似物8-溴环腺苷酸能够在A2受体阻断期间重建破伤风诱导的长时程增强作用;然而，无活性的类似物1，9-双脱氧毛喉素没有影响，表明A2激活对突触传递的影响主要通过细胞内环腺苷酸的调节来介导。由于A1受体对突触传递产生相对于A2受体的相反作用，这些结果表明，A1与A2受体激活的化学计量似乎在海马CA 1区的正常突触传递和长时程增强的调制中发挥重要作用。
Blockade of adenosine A2receptors has been shown to significantly reduce the level of tetanus-induced long-term potentiation in area CA1 of rat hippocampus [Kessey K. et al. (1997) Brain Res. 756, 184–190; Sekino Y. et al. (1991) Biochem. biophys. Res. Commun. 181, 1010–1014]. In the present study, the effects of A2receptor activation and blockade on the modulation of normal synaptic transmission and tetanus-induced long-term potentiation were examined at the Schaffer–CA1 synapse in rat hippocampal slices. A2receptor activation reversibly enhanced synaptic transmission evoked by low-frequency test pulses as measured by the dendritic field excitatory postsynaptic potential. In the presence of A1receptor blockade, A2activation further enhanced the excitatory postsynaptic potential, while A2receptor blockade resulted in a reversible decrease of the excitatory postsynaptic potential. The A2areceptor agonist, CGS21680, had no effect on the excitatory postsynaptic potential, suggesting that tonic activation of A2breceptors contributes to synaptic transmission under normal physiological conditions. Furthermore, we investigated the contribution of A2receptors to the level of tetanus-induced long-term potentiation. Under control conditions, a single tetanus potentiated the excitatory postsynaptic potential by 63.5% relative to baseline 30min post-tetanus. In contrast, tetanus-induced long-term potentiation during A2blockade was 21.3%. A2receptor activation increased the level of tetanus-induced long-term potentiation to 90.2%. Because A2receptors are known to stimulate cyclic-AMP accumulation, the possible involvement of cyclic-AMP was examined. Forskolin, a direct adenylate cyclase activator, and 8-bromo-cyclic-AMP, a membrane-permeable analog of cyclic-AMP, were able to reconstitute tetanus-induced long-term potentiation during A2receptor blockade; however, the inactive analog 1,9-dideoxy-forskolin had no effect, indicating that the effects of A2activation on synaptic transmission were mediated largely through the regulation of intracellular cyclic-AMP. Because A1receptors exert an opposing effect on synaptic transmission relative to A2receptors, these results suggest that the stoichiometry of A1versus A2receptor activation appears to play an important role in the modulation of normal synaptic transmission and long-term potentiation in the CA1 region of the hippocampus.