Regional differences of tachykinin effects on smooth muscle and pacemaker potentials of the stomach, duodenum, ileum and colon of an emetic model, the house musk shrews

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Neuropeptides Pub Date : 2023-02-01 DOI:10.1016/j.npep.2022.102300

Julia Y.H. Liu , Yingyi Deng , Jessica C.M. Hui , Peng Du , Heidi S.H. Ng , Zengbing Lu , Lingqing Yang , Luping Liu , Aleena Khalid , M.P. Ngan , Dexuan Cui , Bin Jiang , S.W. Chan , John A. Rudd

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引用次数: 1

Abstract

Background and aims

The contractile effects of tachykinins on the gastrointestinal tract are well-known, but how they modulate slow-waves, particularly in species capable of emesis, remains largely unknown. We aimed to elucidate the effects of tachykinins on myoelectric and contractile activity of isolated gastrointestinal tissues of the Suncus murinus.

Methods

The effects of substance P (SP), neurokinin (NK)A, NKB and selective NK₁ (CP122,721, CP99,994), NK₂ (SR48,968, GR159,897) and NK₃ (SB218,795, SB222,200) receptor antagonists on isolated stomach, duodenum, ileum and colon segments were studied. Mechanical contractile activity was recorded using isometric force displacement transducers. Electrical pacemaker activity was recorded using a microelectrode array.

Results

Compared with NKA, SP induced larger contractions in stomach tissue and smaller contractions in intestinal segments, where oscillation magnitudes increased in intestinal segments, but not the stomach. CP122,721 and GR159,897 inhibited electrical field stimulation-induced contractions of the stomach, ileum and colon. NKB and NK₃ had minor effects on contractile activity. The inhibitory potencies of SP and NKA on the peristaltic frequency of the colon and ileum, respectively, were correlated with those on electrical pacemaker frequency. SP, NKA and NKB inhibited pacemaker activity of the duodenum and ileum, but increased that of the stomach and colon. SP elicited a dose-dependent contradictive pacemaker frequency response in the colon.

Conclusion

This study revealed distinct effects of tachykinins on the mechanical and electrical properties of the stomach and colon vs. the proximal intestine, providing a unique aspect on neuromuscular correlation in terms of the effects of tachykinin on peristaltic and pacemaker activity in gastrointestinal-related symptoms.

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速激肽对催吐模型麝香鼩胃、十二指肠、回肠和结肠平滑肌和起搏电位影响的区域差异

背景和目的速激肽对胃肠道的收缩作用是众所周知的，但它们如何调节慢波，特别是在能够呕吐的物种中，在很大程度上仍然未知。我们的目的是阐明速激肽对离体鼠胃肠组织的肌电和收缩活性的影响。方法研究P物质（SP）、神经激肽（NK）A、NKB和选择性NK1（CP122721、CP99994）、NK2（SR48968、GR159897）和NK3（SB218795、SB222200）受体拮抗剂对离体胃、十二指肠、回肠和结肠节段的影响。使用等轴测力-位移传感器记录机械收缩活动。使用微电极阵列记录起搏器的电活动。结果与NKA相比，SP引起胃组织收缩较大，肠段收缩较小，肠段振荡幅度增加，但胃没有。CP122721和GR159897抑制电场刺激诱导的胃、回肠和结肠的收缩。NKB和NK3对收缩活性的影响较小。SP和NKA对结肠和回肠蠕动频率的抑制能力分别与对电起搏器频率的抑制力相关。SP、NKA和NKB抑制十二指肠和回肠的起搏器活性，但增加胃和结肠的起搏器活性。SP在结肠中引发剂量依赖性矛盾性起搏器频率反应。结论本研究揭示了速激肽对胃和结肠与近端肠的机械和电学特性的不同影响，为速激肽在胃肠道相关症状中对蠕动和起搏器活性的影响提供了一个独特的神经肌肉相关性方面。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.