Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice
Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice
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DOI：
10.1113/jphysiol.2005.089714
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发表时间：
2005-08-15
影响因子：
5.5
通讯作者：
Blackshaw, LA
中科院分区：
文献类型：
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作者：
Brierley, SM;Carter, R;Blackshaw, LA
腰内脏神经和骶盆神经从结肠向脊髓传递不同的机械感觉信息。在这里，我们确定这些途径是否也在其化疗敏感性和受体表达不同。使用在体外小鼠结肠制备，个别初级传入进行了测试与选择性P2 X和瞬时受体电位香草酸受体1（TRPV 1）受体配体。从结肠逆行标记胸腰段和腰骶段背根神经节（DRG）的传入细胞体，并分析P2 X（3）和TRPV 1样免疫反应性（LI）。40%的LSN传入对α，β-亚甲基腺苷5 '-三磷酸（α，β-meATP; 1 mm）有反应，这种效应是浓度依赖性的，并被P2 X拮抗剂吡啶氧基5-磷酸6-偶氮苯基-2'，4 '-二磺酸（PPADS）（100 μ m）逆转。显著较少的PN传入（7%）对α，β-meATP有反应。相应地，36%的结肠胸腰段DRG神经元显示P2 X（3）-LI，而结肠腰骶段神经元仅为19%。辣椒素（3 μ m）兴奋61%的LSN传入和47%的PN传入; 82%的胸腰椎和50%的腰骶结肠DRG神经元显示TRPV 1-LI。机械不敏感的传入招募的α，β-meATP或辣椒素，几乎是排他性的的LSN。辣椒素反应性的LSN传入显示出显着的机械脱敏后，辣椒素，这并没有发生在辣椒素反应性的PN传入。因此，结肠的LSN和PN途径在它们对已知的伤害性刺激的化学敏感性和它们相应的受体表达方面不同。由于这些途径传递可能与功能性胃肠道疾病症状相关的信息，因此这些结果可能对靶向受体调节的治疗疗效有影响。
Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient receptor potential vanilloid receptor 1 (TRPV1) receptor ligands. Afferent cell bodies in thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely labelled from the colon and analysed for P2X(3)- and TRPV1-Iike immunoreactivity (LI). Forty per cent of LSN afferents responded to alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-meATP; 1 mm), an effect that was concentration dependent and reversed by the P2X antagonist pyridoxyl5-phosphate 6-azophenyl-2',4'-disulphonic acid (PPADS) (100 mu m). Significantly fewer PN afferents (7%) responded to alpha,beta-meATP. Correspondingly, 36% of colonic thoracolumbar DRG neurones exhibited P2X(3)-LI compared with only 19% of colonic lumbosacral neurones. Capsaicin (3 mu m) excited 61% of LSN afferents and 47% of PN afferents; 82% of thoracolumbar and 50% of lumbosacral colonic DRG neurones displayed TRPV1-LI. Mechanically insensitive afferents were recruited by alpha,beta-meATP or capsaicin, and were almost exclusive to the LSN. Capsaicin-responsive LSN afferents displayed marked mechanical desensitization after responding to capsaicin, which did not occur in capsaicin-responsive PN afferents. Therefore, colonic LSN and PN pathways differ in their chemosensitivity to known noxious stimuli and their corresponding receptor expression. As these pathways relay information that may relate to symptoms in functional gastrointestinal disease, these results may have implications for the efficacy of therapies targeting receptor modulation.