Beta 2-adrenergic receptor mediates noradrenergic action to induce cyclic adenosine monophosphate response element-binding protein phosphorylation in satellite glial cells of dorsal root ganglia to regulate visceral hypersensitivity.
Beta 2-adrenergic receptor mediates noradrenergic action to induce cyclic adenosine monophosphate response element-binding protein phosphorylation in satellite glial cells of dorsal root ganglia to regulate visceral hypersensitivity.
复制标题
DOI：
10.1097/j.pain.0000000000002330
复制
发表时间：
2022-01-01
期刊：
影响因子：
7.4
通讯作者：
Qiao LY
中科院分区：
文献类型：
--
作者：
Shen S;Tiwari N;Madar J;Mehta P;Qiao LY
交感神经元流出到背根神经节（DRG）被认为参与交感神经维持的慢性疼痛，这是由去甲肾上腺素（NE）对DRG细胞的作用介导的。本研究结合体内外方法，以确定接受NE作用的DRG细胞类型，并检查DRG中肾上腺素能受体（AR）的细胞类型特异性表达。使用DRG外植体，我们确定NE作用于卫星胶质细胞（SGCs）诱导cAMP反应元件结合（CREB）的磷酸化。使用原代培养的SGCs，我们发现β 2 AR而不是α AR或其他β AR亚型介导NE诱导的CREB磷酸化和CREE促进的荧光素酶转录活性。应用荧光原位杂交和亲和纯化的方法，我们发现β 2 AR在SGCs中表达，而在DRG神经元中不表达。我们进一步研究了β 2 AR表达和CREB磷酸化在结肠炎模型中的体内作用，在该模型中观察到DRG中的交感神经发芽。我们发现，在结肠炎诱导后第7天，胸腰段DRG的SGCs中β 2 AR表达和CREB磷酸化增加。抑制而非增强β 2 AR可减少结肠炎诱导的降钙素基因相关肽（CGRP）释放到脊髓背角和结肠疼痛对结直肠扩张的反应。β 2 AR激活时间延长，DRG神经元CGRP表达增加。这些发现为β 2 AR介导的DRG SGCs交感神经对感觉活动和慢性疼痛的调节提供了分子基础。
Sympathoneuronal outflow into dorsal root ganglia (DRG) is suggested to be involved in sympathetically maintained chronic pain, which is mediated by norepinephrine (NE) action on DRG cells. The present study combined in vitro and in vivo approaches to identify the cell types of DRG that received NE action and examined cell-type specific expression of adrenergic receptors (ARs) in DRG. Using DRG explants, we identified that NE acted on satellite glial cells (SGCs) to induce the phosphorylation of cAMP response element-binding (CREB). Using primarily cultured SGCs, we identified that beta (β)2AR but not alpha (α)AR nor other βAR isoforms mediated NE-induced CREB phosphorylation and CRE-promoted luciferase transcriptional activity. Using fluorescence in situ hybridization and affinity purification of mRNA from specific cell types, we identified that β2AR was expressed by SGCs but not DRG neurons. We further examined β2AR expression and CREB phosphorylation in vivo in a model of colitis in which sympathetic nerve sprouting in DRG was observed. We found that β2AR expression and CREB phosphorylation were increased in SGCs of thoracolumbar DRG on day 7 following colitis induction. Inhibition but not augmentation of β2AR reduced colitis- induced calcitonin gene-related peptide (CGRP) release into the spinal cord dorsal horn and colonic pain responses to colorectal distention. Prolonged activation of β2AR in naïve DRG increased CGRP expression in DRG neurons. These findings provide molecular basis of sympathetic modulation of sensory activity and chronic pain that involves β2AR-mediated signaling in SGCs of DRG.
登录
查看更多内容
影响因子：
4.8
作者：
Gracida, Xicotencatl;Calarco, John A.
通讯作者：
Calarco, John A.
影响因子：
6.2
作者：
Carriba, Paulina;Pardo, Luis;Galea, Elena
通讯作者：
Galea, Elena
影响因子：
3.7
作者：
Deiteren A;van der Linden L;de Wit A;Ceuleers H;Buckinx R;Timmermans JP;Moreels TG;Pelckmans PA;De Man JG;De Winter BY
通讯作者：
De Winter BY
影响因子：
8.8
作者：
Ciszek BP;O'Buckley SC;Nackley AG
通讯作者：
Nackley AG
影响因子：
4.8
作者：
Carter, Bradley S.;Fletcher, Jonathan S.;Thompson, Robert C.
通讯作者：
Thompson, Robert C.