Mechanisms of the White Sea cod Gadus morhua marisalbi (Gadidae) intestinal smooth muscle cholinergic contraction: the contribution of various subtypes of M-cholinergic receptors and Rho-kinase

A.A. Shvetsova, G.V. Morgunova, E.A. Novoderezhkina, V.M. Potekhina, A.A. Kamensky, O.S. Tarasova
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Abstract

The study of the functioning of various body systems in diff erent vertebrates is one of the key tasks of comparative physiology. Teleost fi sh are a large group of vertebrates, however, the mechanisms of functioning of their digestive tract have been studied little and mainly only for such a model object as Danio rerio. The aim of this work was to characterize the participation of various subtypes of M-cholinergic receptors and the enzyme Rho-kinase in the cholinergic contraction of the intestinal smooth muscles of the White Sea cod Gadus morhua marisalbi (Gadidae). A longitudinal strip was excised from the proximal cod intestine and placed in an apparatus for recording contractile responses in the isometric mode. Contractile responses to acetylcholine were ompletely blocked by atropine. Blockade of M3 cholinergic receptors with 4-DAMP resulted in a decrease in acetylcholine-induced contraction compared with the control response. Blockade of M1 receptors with pirenzepine led to a weakening of contraction, less pronounced than with blockade of M3 cholinergic receptors. Blockade of M2-cholinergic receptors with methoctramine did not affect the magnitude of the contractile response. Incubation of preparations with the Rho-kinase inhibitor fasudil was accompanied by a significant decrease in contractile responses compared with the control, as well as a faster decrease in the contraction force after reaching the “peak” of the reaction. Thus, acetylcholine causes contraction of cod intestinal smooth muscle by activating M3- and M1- but not M2-cholinergic receptors. The activity of the Rho-kinase enzyme contributes to the development and maintenance of cod intestinal smooth muscle contraction under the action of acetylcholine. The results obtained are of interest for comparative physiology, may be important for understanding the mechanisms of the damaging effect of environmental factors on the bony fish’ body, as well as for the use of fish as objects of preclinical studies of drugs.
白海鳕鱼肠平滑肌胆碱能收缩的机制:m -胆碱能受体各亚型和rho激酶的贡献
研究不同脊椎动物不同身体系统的功能是比较生理学的关键任务之一。硬骨鱼是一大类脊椎动物,但对其消化道功能机制的研究甚少,主要是针对硬骨鱼这样的模型对象。本研究的目的是研究m -胆碱能受体的不同亚型和rho激酶酶在白海鳕鱼肠平滑肌胆碱能收缩中的作用。从近端肠切除一条纵向条,置于等距模式下记录收缩反应的仪器中。对乙酰胆碱的收缩反应被阿托品完全阻断。与对照反应相比,4-DAMP阻断M3胆碱能受体导致乙酰胆碱诱导的收缩减少。吡仑西平阻断M1受体导致收缩减弱,但不像阻断M3胆碱能受体那么明显。甲氯曲明阻断m2 -胆碱能受体不影响收缩反应的大小。用rho激酶抑制剂法舒地尔孵育的制剂与对照组相比,收缩反应明显下降,并且在达到反应“峰值”后收缩力下降更快。因此,乙酰胆碱通过激活M3-和M1-而不是m2 -胆碱能受体引起鳕鱼肠平滑肌收缩。rho激酶的活性参与了乙酰胆碱作用下鳕鱼肠平滑肌收缩的发展和维持。获得的结果对比较生理学很有兴趣,可能对理解环境因素对硬骨鱼身体的破坏性影响的机制很重要,也可能对将鱼作为药物临床前研究的对象很重要。
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