NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity.
NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity.
复制标题
DOI：
10.1186/1744-8069-5-54
复制
发表时间：
2009-09-22
期刊：
影响因子：
3.3
通讯作者：
Caudle RM
中科院分区：
文献类型：
--
作者：
Suckow SK;Caudle RM
内脏过敏是诊断功能性肠道疾病患者时进行的临床观察。内脏过敏的原因尚不清楚，但被认为是炎症所致。之前我们证明了一组独特的肠神经元，即脊髓传入神经元（CAN），与 NMDA 受体的 NR1 和 NR2D 亚基以及 PAR2 受体共定位。本研究的目的是确定 CAN 上表达的 NMDA 和 PAR2 受体是否会导致炎症后的内脏超敏反应。最近的研究表明，表达瞬时受体电位香草酸-1 (TRPV1) 受体的背根神经节 (DRG) 神经元可介导炎症诱导的内脏超敏反应。因此，为了研究 CAN 参与内脏超敏反应，在炎症和行为测试之前用树脂毒素 (RTX) 损伤表达 TRPV1 受体的 DRG 神经元。 CAN不表达TRPV1受体；因此，它们在注射 RTX 后仍能存活。 RTX 治疗导致结肠中表达 TRPV1 的神经元显着减少，免疫组织化学分析显示，与对照数据相比，RTX 损伤后 CAN 中的肽或受体表达没有变化。行为研究确定，与对照组相比，发炎的非 RTX 和 RTX 动物的球囊压力阈值均降低。免疫组织化学分析表明，CAN 上 NMDA 受体的 NR1 盒、N1 和 C1 在炎症后上调。此外，炎症导致 CAN 上表达的 PAR2 受体激活。我们的数据表明，炎症会导致 NMDA 受体上调，并激活 CAN 上表达的 PAR2 受体。这些变化与非 RTX 和 RTX 病变动物中因结直肠扩张而导致的球囊压力降低有关。因此，这些数据表明 CAN 会导致炎症期间的内脏过敏。
Visceral hypersensitivity is a clinical observation made when diagnosing patients with functional bowel disorders. The cause of visceral hypersensitivity is unknown but is thought to be attributed to inflammation. Previously we demonstrated that a unique set of enteric neurons, colospinal afferent neurons (CANs), co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor. The aim of this study was to determine if NMDA and PAR2 receptors expressed on CANs contribute to visceral hypersensitivity following inflammation. Recently, work has suggested that dorsal root ganglion (DRG) neurons expressing the transient receptor potential vanilloid-1 (TRPV1) receptor mediate inflammation induced visceral hypersensitivity. Therefore, in order to study CAN involvement in visceral hypersensitivity, DRG neurons expressing the TRPV1 receptor were lesioned with resiniferatoxin (RTX) prior to inflammation and behavioural testing. CANs do not express the TRPV1 receptor; therefore, they survive following RTX injection. RTX treatment resulted in a significant decrease in TRPV1 expressing neurons in the colon and immunohistochemical analysis revealed no change in peptide or receptor expression in CANs following RTX lesioning as compared to control data. Behavioral studies determined that both inflamed non-RTX and RTX animals showed a decrease in balloon pressure threshold as compared to controls. Immunohistochemical analysis demonstrated that the NR1 cassettes, N1 and C1, of the NMDA receptor on CANs were up-regulated following inflammation. Furthermore, inflammation resulted in the activation of the PAR2 receptors expressed on CANs. Our data show that inflammation causes an up-regulation of the NMDA receptor and the activation of the PAR2 receptor expressed on CANs. These changes are associated with a decrease in balloon pressure in response to colorectal distension in non-RTX and RTX lesioned animals. Therefore, these data suggest that CANs contribute to visceral hypersensitivity during inflammation.
登录
查看更多内容
DOI：
10.1152/ajpgi.00351.2007
发表时间：
2008-01-01
影响因子：
4.5
作者：
De Schepper, H. U.;De Man, J. G.;De Winter, B. Y.
通讯作者：
De Winter, B. Y.
影响因子：
3.3
作者：
Doyle, CA;Hunt, SP
通讯作者：
Hunt, SP
影响因子：
5.5
作者：
Lawson, SN;Crepps, BA;Perl, ER
通讯作者：
Perl, ER
影响因子：
3.3
作者：
Suckow, S. K.;Caudle, R. M.
通讯作者：
Caudle, R. M.
影响因子：
5.3
作者：
Jones, RCW;Xu, LJ;Gebhart, GF
通讯作者：
Gebhart, GF