Differential functional role of purinergic and nitrergic inhibitory cotransmitters in human colonic relaxation
Differential functional role of purinergic and nitrergic inhibitory cotransmitters in human colonic relaxation
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DOI：
10.1111/apha.12408
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发表时间：
2014-12-01
影响因子：
6.3
通讯作者：
Jimenez, M.
中科院分区：
文献类型：
--
作者：
Mane, N.;Gil, V.;Jimenez, M.
目的：从肠抑制性运动神经元释放出一氧化氮（NO），并负责结肠平滑肌松弛。然而，在人类结肠中，神经刺激频率如何影响这种共传递过程和连接后反应尚未得到系统的表征。方法采用不同的电场刺激方案对36例患者结肠条的抑制连接电位（IJP）和相应的弛豫进行了动力学研究。结果单脉冲诱发快速IJP (IJPf(MAX)=-27.61.6 mv)，对P2Y(1)拮抗剂MRS2500 m敏感，随着频率的增加，IJPf（MAX）下降，在高频（IJPf=-3.7 +/- 0.6mV）处残留超极化。因此，低频电激引起嘌呤能瞬态松弛，在高频下不能维持。在嘌呤能分解期间加入P2Y(1)激动剂MRS2365 10m未引起任何超极化。蛋白激酶C （PKC）是一种假定的P2Y(1)脱敏剂，在激活时能够降低IJPf的振幅，但PKC抑制剂不能改变这种下降。需要高于0.60 +/- 0.15Hz的频率才能引起持续的氮能超极化，该超极化逐渐增加，在高频时达到ijp =-13 +/- 0.4mV，并导致自发运动的持续抑制。结论刺激频率的变化可能模拟神经元放电，将在连接后决定不同功能作用下的嘌呤能和氮能反应。一氧化氮将负责生理过程中所需的持续松弛，如储存，而嘌呤能神经递质将在推进等过程中引起急剧的短暂松弛。
AimATP and nitric oxide (NO) are released from enteric inhibitory motor neurones and are responsible for colonic smooth muscle relaxation. However, how frequency of neural stimulation affects this cotransmission process and the post-junctional responses has not been systematically characterized in the human colon.MethodsThe dynamics of inhibitory cotransmission were studied using different protocols of electrical field stimulation (EFS) to characterize the inhibitory junction potentials (IJP) and the corresponding relaxation in colonic strips obtained from 36 patients.ResultsSingle pulses elicited a fast IJP (IJPf(MAX)=-27.61.6mV), sensitive to the P2Y(1) antagonist MRS2500 1m, that ran down with frequency increase leaving a residual hyperpolarization at high frequencies (IJPf=-3.7 +/- 0.6mV). Accordingly, low frequencies of EFS caused purinergic transient relaxations that cannot be maintained at high frequencies. Addition of the P2Y(1) agonist MRS2365 10m during the purinergic rundown did not cause any hyperpolarization. Protein kinase C (PKC), a putative P2Y(1) desensitizator, was able to reduce the amplitude of the IJPf when activated, but the rundown was not modified by PKC inhibitors. Frequencies higher than 0.60 +/- 0.15Hz were needed to evoke a sustained nitrergic hyperpolarization that progressively increased reaching IJPs=-13 +/- 0.4mV at high frequencies and leading to a sustained inhibition of spontaneous motility.ConclusionChanges in frequency of stimulation possibly mimicking neuronal firing will post-junctionally determine purinergic vs. nitrergic responses underlying different functional roles. NO will be responsible for sustained relaxations needed in physiological processes such as storage, while purinergic neurotransmission evoking sharp transient relaxations will be dominant in processes such as propulsion.