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Functional expression of 5-HT7 receptor on the substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice

机译:5-HT7受体在小鼠三叉神经尾核明胶神经元神经元上的功能表达

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The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc; medullary dorsal horn) receives and processes orofacial nociceptive inputs, and serotonergic fibers involved in the descending modulation of nociception are more densely distributed in the superficial laminae of the Vc. This study investigated the direct effects of 5-HT1A/7 receptor agonist 8-OH-DPAT on SG neurons of the Vc to assess functional expression of the 5-HT7 receptor using gramicidin-perforated patch-clamp in postnatal day (PND) 5-84 male mice. Of the 70 SG neurons tested, bath application of 8-OH-DPAT (30 μM) induced depolarization (n=33), hyperpolarization (n=16) or no response (n=21). In another 10 SG neurons, 8-OH-DPAT in the presence of 5-HT1A receptor antagonist WAY-100635 (1 μM) elicited either depolarization (n=6) or no response (n=4); hyperpolarization was not observed. The 8-OH-DPAT-induced depolarization was significantly blocked by the selective 5-HT7 receptor antagonist SB-269970 (10 μM; n=8), but not by WAY-100635 (1 μM; n=5). The depolarizing effect of 8-OH-DPAT was maintained in the presence of TTX, CNQX, AP5, picrotoxin, and strychnine, indicating direct postsynaptic action of 8-OH-DPAT on SG neurons (n=6). 5-HT7 receptor mRNA was also detected in five of 21 SG neurons by single-cell RT-PCR. The mean amplitude of 8-OH-DPAT-induced depolarization in PND 5-21 mice (n=21) was significantly larger than that in PND 22-84 mice (n=12), although the proportion of SG neurons responding to 8-OH-DPAT by depolarization did not differ significantly between two age groups of mice. These results indicate that 5-HT7 receptors are functionally expressed in a subpopulation of SG neurons of the Vc and activation of 5-HT7 receptors plays an important role in modulating orofacial nociceptive processing in the SG neurons of the Vc.
机译:三叉神经尾核(Vc;延髓背角)的明胶质(SG)接收并处理口面伤害感受输入,参与伤害感受递减调节的血清素能纤维更密集地分布在Vc的表层。这项研究调查了5-HT1A / 7受体激动剂8-OH-DPAT对Vc的SG神经元的直接作用,以评估在产后一天(PND)5中使用了绞链霉菌素穿孔的膜片钳对5-HT7受体的功能表达。 84只雄性小鼠。在测试的70个SG神经元中,洗澡应用8-OH-DPAT(30μM)会引起去极化(n = 33),超极化(n = 16)或无反应(n = 21)。在另外10个SG神经元中,在5-HT1A受体拮抗剂WAY-100635(1μM)存在下的8-OH-DPAT引起去极化(n = 6)或无反应(n = 4);没有观察到超极化。选择性5-HT7受体拮抗剂SB-269970(10μM; n = 8)显着阻断了8-OH-DPAT诱导的去极化作用,而WAY-100635(1μM; n = 5)则没有明显作用。在存在TTX,CNQX,AP5,微毒素和士的宁的情况下,可以保持8-OH-DPAT的去极化作用,表明8-OH-DPAT对SG神经元具有直接的突触后作用(n = 6)。还通过单细胞RT-PCR在21个SG神经元中的五个神经元中检测到5-HT7受体mRNA。尽管SG神经元对8位神经元有响应的比例,但PND 5-21小鼠(n = 21)中8-OH-DPAT引起的去极化的平均幅度明显大于PND 22-84小鼠(n = 12)中的去极化。在两个年龄段的小鼠之间,通过去极化的OH-DPAT没有显着差异。这些结果表明5-HT 7受体在Vc的SG神经元的亚群中功能性表达,并且5-HT 7受体的活化在调节Vc的SG神经元的口部伤害感受过程中起重要作用。

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