Urothelium releases neuro-like chemical substances for micturition reflex

先前的研究表明，激活尿路上皮细胞的α _1肾上腺素能受体释放神经递质。本研究旨在确定α <1D>肾上腺素能受体是否在大鼠膀胱尿路上皮中表达，以及抑制这些受体是否影响反射性排尿。实验采用雌性Wistar大鼠。Western blot检测受体表达。通过膀胱造影、膀胱腔内ATP浓度测量和传入神经记录来研究受体激活的影响。将α <1D>拮抗剂萘托地尔（0.75 ~ 1.66 mg/kg）静脉注入颈外静脉。Westernblot和免疫组化检测尿路上皮组织α _<1D>肾上腺素能受体的表达。α _<1D>受体拮抗剂萘托地尔延长了清醒大鼠连续输注膀胱造影时的收缩间期（ICI，为对照组的143%），并抑制了膀胱内输注醋酸（0.1%）对ICI的兴奋作用（220%）。Naftopidil抑制膀胱膨胀（32.0%）或醋酸输注（30.4%）引起的膀胱传入神经活动，降低膀胱膨胀时膀胱灌注液中ATP水平（36.6%）。内源性儿茶酚胺似乎作用于尿路上皮α _<1D>受体，促进机械敏感性膀胱传入神经活动和反射性排尿。

Previous studies revealed that activation of alpha_1 adrenergic receptors in urothelial cells releases neurotransmitters. This study was undertaken to determine if alpha_<1D> adrenergic receptors are expressed in the urothelium of the rat bladder and if inhibition of these receptors affects reflex voiding. Female Wistar rats were used for the experiments. Receptor expression was evaluated by Western blot. The effects of receptor activation were studied using cystometrograms, measurement of ATP concentrations in the bladder lumen and afferent nerve recording. The alpha_<1D> antagonist, naftopidil (0.75-1.66 mg/kg) was administered intravenously into the external jugular vein. Expression of alpha_<1D> adrenergic receptors was detected in urothelial tissue with Westernblot and Immunohistochemistry. The alpha_<1D> receptor antagonist, naftopidil prolonged the intercontraction interval (ICI, 143 % of the control) during continuous infusion cystometrograms in conscious rats, and suppressed the excitatory effect of intravesical infusion of acetic acid (0.1 %) on the ICI (220 %). Naftopidil inhibited bladder afferent nerve activity induced by bladder distension (32.0%) or acetic acid infusion (30.4 %) and reduced the ATP levels in the bladder perfusate during bladder distension (36.6 %). Endogenous catecholamines appear to act on alpha_<1D> receptors in the urothelium to facilitate the mechano-sensitive bladder afferent nerve activity and reflex voiding.