Release of glutamate and CGRP from trigeminal ganglion neurons: Role of calcium channels and 5-HT1 receptor signaling.

Release of glutamate and CGRP from trigeminal ganglion neurons: Role of calcium channels and 5-HT1 receptor signaling.
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DOI:
10.1186/1744-8069-4-12
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发表时间:
2008-04-16
期刊:
影响因子:
3.3
通讯作者:
Hurley, Joyce H.
Hurley, Joyce H.
中科院分区:
医学3区
文献类型:
--
作者:
Xiao, Yan;Richter, Judith A.;Hurley, Joyce H.

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三叉神经细胞中神经递质谷氨酸和降钙素基因相关肽(CGRP)的异常释放与偏头痛有关。电压门控的P/Q型钙通道在控制神经递质释放方面起着关键作用,并与家族性偏瘫有关。因此,我们研究了电压依赖性钙通道在控制培养的大鼠三叉神经节神经元谷氨酸和降钙素基因相关肽释放中的重要性。5-羟色胺能通路可能与偏头痛有关,因为Triptans是一类5-HT1受体激动剂,对偏头痛的治疗有效,其有效性可能是由于抑制了三叉神经细胞的神经递质释放。我们还研究了5-羟色胺受体激活对培养的三叉神经细胞释放谷氨酸和降钙素基因相关肽的影响。P/Q通道、N通道和L通道分别介导钾刺激的谷氨酸和降钙素基因相关肽的大量释放。我们发现5-羟色胺显著抑制钾刺激的谷氨酸和降钙素基因相关肽的释放。5-羟色胺能抑制CGRP和谷氨酸的释放可被百日咳毒素和5-HT1B/1D拮抗剂NAS-181阻断。5-羟色胺3拮抗剂Y-25130和5-羟色胺2B/2C拮抗剂SB 200646不影响降钙素基因相关肽的刺激释放。这些结果表明,三叉神经细胞谷氨酸和降钙素基因相关肽的释放均受钙通道的调控,并受5-羟色胺信号的调节,这种调节方式依赖于百日咳毒素,并可能通过5-HT1受体信号。这是培养的三叉神经细胞释放谷氨酸的第一个特征。
The aberrant release of the neurotransmitters, glutamate and calcitonin-gene related peptide (CGRP), from trigeminal neurons has been implicated in migraine. The voltage-gated P/Q-type calcium channel has a critical role in controlling neurotransmitter release and has been linked to Familial Hemiplegic Migraine. Therefore, we examined the importance of voltage-dependent calcium channels in controlling release of glutamate and CGRP from trigeminal ganglion neurons isolated from male and female rats and grown in culture. Serotonergic pathways are likely involved in migraine, as triptans, a class of 5-HT1 receptor agonists, are effective in the treatment of migraine and their effectiveness may be due to inhibiting neurotransmitter release from trigeminal neurons. We also studied the effect of serotonin receptor activation on release of glutamate and CGRP from trigeminal neurons grown in culture. P/Q-, N- and L-type channels each mediate a significant fraction of potassium-stimulated release of glutamate and CGRP. We determined that 5-HT significantly inhibits potassium-stimulated release of both glutamate and CGRP. Serotonergic inhibition of both CGRP and glutamate release can be blocked by pertussis toxin and NAS-181, a 5-HT1B/1D antagonist. Stimulated release of CGRP is unaffected by Y-25130, a 5-HT3 antagonist and SB 200646, a 5-HT2B/2C antagonist. These data suggest that release of both glutamate and CGRP from trigeminal neurons is controlled by calcium channels and modulated by 5-HT signaling in a pertussis-toxin dependent manner and probably via 5-HT1 receptor signaling. This is the first characterization of glutamate release from trigeminal neurons grown in culture.
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