Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder
Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder
复制标题
DOI：
10.1113/jphysiol.2001.013469
复制
发表时间：
2002-06-01
影响因子：
5.5
通讯作者：
Burnstock, G
中科院分区：
文献类型：
--
作者：
Rong, W;Spyer, KM;Burnstock, G
有人提出，细胞外ATP可能通过激活配体门控离子通道（P2X受体）参与内脏机械感觉传导。在这项研究中，我们研究了P2X(3)激动剂α， β -亚甲基ATP （α， β -肉ATP）和拮抗剂2',3'- o -三硝基苯基ATP （TNP-ATP）对体外小鼠膀胱-骨盆神经制剂支配膀胱的骨盆传入神经的影响。膀胱内应用α， β -肉atp （0.01 -1 mM）以浓度依赖的方式增加多纤维放电。激动剂增强，而TNP-ATP （0.03 mm）减弱，多纤维对膀胱膨胀的反应。单单元分析显示，膀胱内α -肉atp （1 mM, 0.1 ml）可诱导高阈值（HT）纤维（约15 mmHg，已知与伤害性事件有关）和低阈值（LT）纤维（< 15 mmHg，可能与非伤害性事件有关）放电。绝大多数（21/ 22,95.5%）的HT纤维对膀胱膨胀的反应增强，暴露于激动剂后阈值显著降低，峰值反应增加。另一方面，59.7%（46/77）的LT纤维在α， β -肉atp存在时表现出更大的峰值和稍微降低的膀胱膨胀反应阈值。另外11种“沉默”纤维在接触α、β -肉atp后变得机械敏感。TNP-ATP （0.03 mM）不影响LT纤维的阈值，但降低了部分（22/51,43.1%）LT纤维的峰值响应。相反，拮抗剂导致大多数（13/16,81.3%）HT纤维的阈值显著升高，峰值活性降低。这些结果支持了P2X(3)受体介导的机制有助于膀胱中伤害性和非伤害性（生理）机械感觉传导的观点。
It has been proposed that extracellular ATP may be involved in visceral mechanosensory transduction by activating ligand-gated ion channels (P2X receptors). In this study, we have investigated the effects of the P2X(3) agonist alpha,beta-methylene ATP (alpha,beta-meATP) and antagonist 2',3'-O-trinitrophenyl-ATP (TNP-ATP) on pelvic afferents innervating the urinary bladder using an in vitro mouse bladder-pelvic nerve preparation. Intravesical application of alpha,beta-meATP (0.03-1 mM) increased multifibre discharges in a concentration-dependent manner. The agonist potentiated, whereas TNP-ATP (0.03 mm) attenuated, the multifibre responses to bladder distensions. Single-unit analysis revealed that both high threshold (HT) fibres (> 15 mmHg; known to be associated with nociception) and low threshold (LT) fibres (< 15 mmHg; probably associated with non-nociceptive events) could be induced to discharge by intravesical alpha,beta-meATP (1 mM, 0.1 ml). The response of the vast majority (21/22, 95.5 %) of HT fibres to bladder distensions was enhanced with a significantly reduced threshold and an increased peak response after exposure to the agonist. On the other hand, 59.7 % (46/77) of LT fibres showed a greater peak and a slightly reduced threshold for response to bladder distension in the presence of alpha,beta-meATP. An additional 11 'silent' fibres became mechanosensitive after exposure to alpha,beta-meATP. TNP-ATP (0.03 mM) did not affect the threshold of LT fibres, but it reduced the peak response of some (22/51, 43.1 %) LT fibres. Conversely, the antagonist resulted in a markedly elevated threshold and reduced peak activity in the majority (13/16, 81.3 %) of HT fibres. The results support the view that P2X(3) receptor-mediated mechanisms contribute to both nociceptive and non-nociceptive (physiological) mechanosensory transduction in the urinary bladder.