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首页> 外文期刊>Life sciences >CDP-choline-induced contractions in the mouse gastric fundus through purinoceptors and Rho/Rho-kinase signalling.
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CDP-choline-induced contractions in the mouse gastric fundus through purinoceptors and Rho/Rho-kinase signalling.

机译：CDP-胆碱通过嘌呤受体和Rho / Rho激酶信号传导诱导小鼠胃底收缩。

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AIMS: This study aimed to investigate the effects of cytidine-5'-diphosphocholine (CDP-choline), an endogenous lipid precursor, on the reactivity of the mouse gastric fundus and to determine the mechanism(s) mediating its effects. MAIN METHODS: Possible contractile effect of CDP-choline (10(-5)-10(-2)M) was investigated in the absence and presence of a muscarinic receptor antagonist, atropine (3 x 10(-6)M), an acetylcholine esterase inhibitor, physostigmine (10(-6)M), a Na(+) channel blocker, tetrodotoxin (TTX, 3 x 10(-6)M), a Rho-kinase inhibitor, Y-27632 (10(-5) M), a purinoceptor antagonist, suramin (2 x 10(-4)M), a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NA, 3 x 10(-4)M), a Ca(2+) channel blocker, nifedipine (10(-6)M), an alpha(7) nicotinic receptor antagonist, methyllycaconitine citrate (MLA, 10(-6)M) and a G protein (G(i/o)) inhibitor, pertussis toxin (PTX, 2 mug/ml). The metabolites of CDP-choline, namely choline (10(-4)-10(-2)M), cytidine 5'-triphosphate (CTP, 10(-5)-10(-2)M), cytidine (10(-5)-10(-2)M) and cytidine monophosphate (CMP, 10(-3)-10(-2)M) were also tested. Besides, phosphorylation of MYPT1, which indicates Rho-kinase activity, was also detected. KEY FINDINGS: CDP-choline produced contractions in a concentration-dependent manner. The contractions were not affected by atropine, physostigmine, TTX, PTX, MLA or L-NA. However, Y-27632, suramin or nifedipine partly reduced these contractions. CDP-choline increased phosphorylation of MYPT1. Among CDP-choline metabolites, cytidine had no contractile effects. However, choline induced considerable contractions, which were sensitive to atropine. CMP and CTP had also contractile activity, comparable to that of CDP-choline. SIGNIFICANCE: These results suggest that CDP-choline produced contraction through, at least in part, purinoceptors and Rho/Rho-kinase signalling in the mouse gastric fundus.
机译：目的：本研究旨在研究内源性脂质前体胞苷5'-二磷酸胆碱（CDP-胆碱）对小鼠胃底反应性的影响，并确定介导其作用的机制。主要方法：在不存在毒蕈碱受体拮抗剂阿托品（3 x 10（-6）M），不存在毒蕈碱受体拮抗剂的情况下，研究了CDP-胆碱（10（-5）-10（-2）M）可能的收缩作用。乙酰胆碱酯酶抑制剂，毒扁豆碱（10（-6）M），Na（+）通道阻滞剂，河豚毒素（TTX，3 x 10（-6）M），Rho激酶抑制剂，Y-27632（10（-5 ）M），嘌呤受体拮抗剂，苏拉明（2 x 10（-4）M），一氧化氮合酶抑制剂，N（G）-硝基-L-精氨酸（L-NA，3 x 10（-4）M） ，Ca（2+）通道阻滞剂，硝苯地平（10（-6）M），α（7）烟碱样受体拮抗剂，柠檬酸甲基卡卡尼碱（MLA，10（-6）M）和G蛋白（G（i / o））抑制剂，百日咳毒素（PTX，2杯/毫升）。 CDP-胆碱的代谢产物，即胆碱（10（-4）-10（-2）M），胞苷5'-三磷酸（CTP，10（-5）-10（-2）M），胞苷（10（还测试了-5）-10（-2）M）和单磷酸胞苷（CMP，10（-3）-10（-2）M）。此外，还检测到指示Rho激酶活性的MYPT1的磷酸化。主要发现：CDP-胆碱以浓度依赖性方式产生收缩。收缩不受阿托品，毒扁豆碱，TTX，PTX，MLA或L-NA的影响。但是，Y-27632，苏拉明或硝苯地平可以部分减轻这些收缩。 CDP-胆碱增加MYPT1的磷酸化。在CDP-胆碱代谢产物中，胞苷没有收缩作用。然而，胆碱引起大量收缩，这对阿托品敏感。 CMP和CTP也具有与CDP胆碱相当的收缩活性。意义：这些结果表明，CDP-胆碱至少部分通过小鼠胃底的嘌呤受体和Rho / Rho激酶信号传导产生了收缩。

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