Inhibitory actions of calcitonin gene-related peptide and capsaicin: evidence for local axonal reflexes in the bladder wall
Inhibitory actions of calcitonin gene-related peptide and capsaicin: evidence for local axonal reflexes in the bladder wall
复制标题
DOI：
10.1111/j.1464-410x.2005.05268.x
复制
发表时间：
2005-01-01
影响因子：
4.5
通讯作者：
Gillespie, JI
中科院分区：
文献类型：
--
作者：
Gillespie, JI
目的探讨辣椒素的作用及其释放的神经递质（P物质和降钙素基因相关肽，CGRP）对毒蕈碱刺激在整个离体豚鼠膀胱中产生的阶段性收缩活动的影响，材料与方法：所有实验均采用离体的雌性大鼠膀胱标本豚鼠（270-300 g）。通过尿道将膀胱插管以测量膀胱内压，并将其悬浮在含有33-35 ℃的氧化台氏溶液的加热室中。将所有药物加入到溶液中浸泡近腔表面。（10 μ mol/L）对整个离体膀胱的M刺激引起的时相活动的频率和幅度的复杂变化;一种包括频率上升的活动的初始爆发，幅度和频率降低的第二阶段，以及瞬态幅度恢复且频率增加的第三阶段。辣椒素对烟碱配体洛贝林（30 μ mol/L）产生的相活性没有影响。由于辣椒素释放感觉神经的神经递质含量，实验探索CGRP和P物质对毒蕈碱诱导的活动的作用。CGRP（3-30 nmol/L）可降低时相活动的振幅并减慢其频率。在冲洗掉CGRP后，瞬时活动的幅度和频率恢复，并且频率在刺激前的水平以上瞬时增加。也有证据表明，对CGRP的脱敏重复应用。与此相反，P物质（100-300 nmol/L）的瞬变的频率增加，而去除它有一个抑制的幅度和frequency.CONCLUSIONS这些结果表明，豚鼠膀胱壁感觉神经末梢释放的神经递质影响相位活动。直接应用CGRP抑制相位活动，而P物质是兴奋性的，表明这些神经递质的具体贡献。CGRP刺激后的兴奋和P物质的抑制可能表明这些神经递质反馈到感觉神经上，以诱导递质释放。两者合计，这些观察结果表明膀胱壁中存在局部反射，其中传入感觉纤维的轴突侧支支配膀胱壁中负责产生阶段性活动的起搏器机制。这种反射在膀胱的生理和病理生理可能的重要性进行了讨论。
OBJECTIVES To explore the actions of capsaicin and the neurotransmitters released by capsaicin (substance P and calcitonin gene-related peptide, CGRP) on the phasic contractile activity generated in the whole isolated guinea pig bladder by muscarinic stimulation, and to examine the hypothesis that collateral fibres of sensory axons contribute to a local reflex in the bladder wall.MATERIALS AND METHODS All experiments used whole isolated bladders from female guinea pigs (270-300 g). Bladders were cannulated via the urethra to measure intravesical pressure and suspended in a heated chamber containing oxygenated Tyrode's solution at 33-35 degreesC. All drugs were added to the solution bathing the abluminal surface.RESULTS Application of capsaicin (10 mumol/L) to the whole isolated bladder resulted in complex changes in the frequency and amplitude of phasic activity generated by muscarinic stimulation; an initial burst of activity involving a rise in frequency, a second phase of reduced amplitude and frequency and a third phase where the amplitude of the transients recovered and the frequency increased. Capsaicin had no effect on the phasic activity generated by the nicotinic ligand lobeline (30 mumol/L. As capsaicin releases the neurotransmitter content of the sensory nerves, experiments explored the actions of CGRP and substance P on the muscarinic-induced activity. CGRP (3-30 nmol/L) reduced the amplitude and slowed the frequency of the phasic activity. On washing off CGRP the amplitude and frequency of the transient activity recovered and there was a transient increase in frequency above the levels before stimulation. There was also evidence of a desensitization to CGRP on repeated application. In contrast, substance P (100-300 nmol/L) increased the frequency of the transients, while on removing it there was an inhibition of both amplitude and frequency.CONCLUSIONS These results suggest that neurotransmitters released from sensory nerve endings in the guinea pig bladder wall affect phasic activity. The direct application of CGRP inhibited phasic activity while substance P was excitatory, indicating the specific contributions of these neurotransmitters. The excitation after stimulation with CGRP and inhibition with substance P may indicate that these neurotransmitters feed back on the sensory nerves to induce transmitter release. Taken together, these observations suggest the presence of a local reflex in the bladder wall, where axon collaterals of afferent sensory fibres innervate the pacemaker mechanism in the bladder wall responsible for generating phasic activity. The possible importance of this reflex in the physiology and pathophysiology of the bladder is discussed.