Substance P and CGRP mediate motor response of rabbit colon to capsaicin.

Substance P and CGRP mediate motor response of rabbit colon to capsaicin.
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DOI:
10.1152/ajpgi.1990.259.5.g889
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发表时间:
1990-11
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
E. Mayer;C. Koelbel;W. Snape;V. Eysselein;H. Ennes;A. Kodner
E. Mayer;C. Koelbel;W. Snape;V. Eysselein;H. Ennes;A. Kodner
中科院分区:
其他
文献类型:
--
作者:
E. Mayer;C. Koelbel;W. Snape;V. Eysselein;H. Ennes;A. Kodner

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位于哺乳动物肠壁的初级传入神经末梢可能在胃肠运动的区域特异性调节中发挥作用。在本研究中,我们试图描述辣椒素(CAP)从这些传入神经释放的神经肽对兔远端结肠平滑肌收缩活动的影响。CAP引起乙酰胆碱的释放和P物质(SP)和降钙素基因相关肽(CGRP)的免疫反应性从肌被。CAP引起纵向肌肉收缩的剂量依赖性瞬时刺激,随后是自发但非刺激性收缩活动的长期抑制。初始刺激被SP拮抗剂Spantide和阿托品消除。重复暴露于CGRP的肌肉的抑制作用降低。CGRP对纵肌和环肌自发性收缩的影响不同。在纵向肌肉中,刺激之前是短暂的抑制,而在环形肌肉中,只看到抑制。这两种效果都对河豚毒素有抵抗力。循环而不是纵向肌肉反复暴露于CGRP导致肽的抑制作用消失。外源性CGRP对SP和氨甲酰胆碱引起的收缩反应仅有微弱的拮抗作用。这些研究结果表明,在兔结肠中,至少有以下两种神经肽从CAP敏感的神经纤维中释放:神经激肽肽从位于肌间神经丛内的神经末梢和CGRP从可能位于环形肌层内的末梢。
Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.