Somatostatin receptors differentially affect spontaneous epileptiform activity in mouse hippocampal slices
Somatostatin receptors differentially affect spontaneous epileptiform activity in mouse hippocampal slices
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DOI：
10.1111/j.1460-9568.2004.03741.x
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Bagnoli, P
中科院分区：
文献类型：
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作者：
Cammalleri, M;Cervia, D;Bagnoli, P
生长抑素-14 [生长激素释放抑制因子 (SRIF)] 可降低海马癫痫样活动，但对其特定受体 (sst(1-5)) 的作用知之甚少。我们使用野生型 (WT) 和 sst(1) 或 sst(2) 敲除 (KO) 小鼠的海马切片，重点研究 sst(1) 和 sst(2) 在介导 SRIF 调节癫痫中的作用。在应用 SRIF 化合物之前和之后，从 CA3 区域记录由含有 4-氨基吡啶的无 Mg2+ 介质诱导的癫痫样放电。在 WT 小鼠中，SRIF 和 sst(1) 激动剂 CH-275 可减少癫痫，而用其拮抗剂 SRA-880 阻断 sst(1) 可增加爆发放电。 sst(2) 的激活不会影响爆发频率，除非其激动剂奥曲肽与 SRA-880 一起使用，这表明 sst(1) 掩盖了 sst(2) 介导的癫痫调节。在 sst(1) KO 小鼠中： (i) 爆发频率低于 WT； (ii) SRIF、CH-275 和 SRA-880 对癫痫无效，(iii) 奥曲肽也没有效果，而用拮抗剂 D-Tyr(8) Cyn 154806 阻断 sst(2) 会增加爆发频率。在 sst(2) KO 小鼠中，SRIF 配体的作用与 WT 中的相似。在sst(1) KO小鼠的整个海马中，sst(2) mRNA、蛋白质和结合比WT中更高，并且CA3分区的逆转录聚合酶链反应证实了sst(2)信使的增加。我们得出结论，sst(1) 介导 SRIF 的抑制作用，并且 sst(1) 和 sst(2) 之间的相互作用可能阻止 sst(2) 对癫痫的调节。我们认为，在 sst(1) KO 小鼠中，过度表达 sst(2) 的激活会降低突发频率，表明 sst(2) 密度代表 sst(2) 介导的癫痫调节的速率限制因素。
Somatostatin-14 [somatotropin release-inhibiting factor (SRIF)] reduces hippocampal epileptiform activity but the contribution of its specific receptors (sst(1-5)) is poorly understood. We have focused on the role of sst(1) and sst(2) in mediating SRIF modulation of epilepsy using hippocampal slices of wild-type (WT) and sst(1) or sst(2) knockout (KO) mice. Recordings of epileptiform discharge induced by Mg2+-free medium with 4-aminopyridine were performed from the CA3 region before and after the application of SRIF compounds. In WT mice, SRIF and the sst(1) agonist CH-275 reduce epilepsy whereas sst(1) blockade with its antagonist SRA-880 increases the bursting discharge. Activation of sst(2) does not affect the bursting frequency unless its agonist octreotide is applied with SRA-880, indicating that sst(1) masks sst(2)-mediated modulation of epilepsy. In sst(1) KO mice: (i) the bursting frequency is lower than in WT; (ii) SRIF, CH-275 and SRA-880 are ineffective on epilepsy and (iii) octreotide is also devoid of effects, whereas blockade of sst(2) with the antagonist D-Tyr(8) Cyn 154806 increases the bursting frequency. In sst(2) KO mice, the SRIF ligand effects are similar to those in WT. In the whole hippocampus of sst(1) KO mice, sst(2) mRNA, protein and binding are higher than in WT and reverse transcription-polymerase chain reaction of the CA3 subarea confirms an increase of the sst(2) messenger. We conclude that sst(1) mediates inhibitory actions of SRIF and that interactions between sst(1) and sst(2) may prevent sst(2) modulation of epilepsy. We suggest that, in sst(1) KO mice, activation of over-expressed sst(2) reduces the bursting frequency, indicating that sst(2) density represents the rate-limiting factor for sst(2)-mediated modulation of epilepsy.