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EFFECTS OF IN VITRO 5-HT1 RECEPTOR ACTIVATION IN GUINEA PIG TRACHEA

机译:豚鼠气管内5-HT1受体激活的影响

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5-hydroxytryptamine (5-HT) has been reported to show some effects in respiratory tissues by activation of different subtype receptors. It has been demonstrated that 5-HT2 receptor activation causes in vivo and in vitro airways contraction and enhances effects of cholinergic nerve-mediated responses, whereas 5-HT1 receptor activation seems to be related to a relaxant effect. Moreover, in isolated guinea pig ascendens colon preparations 5-HT1 activation causes relaxation by involvement of nitric oxide (NO). The aim of this study was to investigate the effects of 5-HT1 receptor activation in guinea pig trachea as well as NO probable role in this activation. In tissues pretreated with both ketanserin (10 mu M), an antagonist of 5-HT2 receptors, and ondansetron (10 mu M) an antagonist of 5-HT3 receptors, 5-HT (from 10 nM to 10 mM) relaxed guinea pig trachea precontracted with acetylcholine (ACh, 100 mu M). Carboxamidotryptamine (5-CT, from 10 nM to 10 mM), an agonist of 5-HT1 receptors, as well relaxed guinea pig trachea precontracted with ACh (100 mu M). A pretreatment with NAN-190 (from 10 nM to 100 mu M), a 5-HT1A selective antagonist, reduced the 5-HT and 5-CT relaxant effects but only at very high concentrations. Finally, a pretreatment with L-nitro-arginine-methyl-ester (L-NAME, 1 mM), an inhibitor of NO-synthase, and L-arginine (L-ARG, 1 mM), a precursor of NO synthesis, did not modify 5-HT and 5-CT responses in guinea pig trachea. In conclusion, this study suggests a 5-HT relaxant activity in guinea pig trachea via a 5-HT1 receptor activation without any NO pathway involvement. However, further investigations are needed to clarify which 5-HT1 receptor subtype is involved in 5-HT relaxant effect. [References: 21]
机译:据报道5-羟色胺(5-HT)通过激活不同的亚型受体在呼吸道组织中显示出某些作用。已经证明5-HT 2受体活化引起体内和体外气道收缩并增强胆碱能神经介导的反应的作用,而5-HT 1受体活化似乎与松弛作用有关。此外,在分离的豚鼠升天结肠中,5-HT1的激活会因一氧化氮(NO)的参与而引起松弛。这项研究的目的是调查5-HT1受体激活在豚鼠气管中的作用以及NO在这种激活中的可能作用。在同时使用5-HT2受体拮抗剂ketanserin(10μM)和5-HT3受体拮抗剂ondansetron(10μM)预处理的组织中,将5-HT(10 nM至10 mM)的豚鼠气管舒张与乙酰胆碱(ACh,100μM)预包羧酰胺基色胺(5-CT,从10 nM到10 mM),是5-HT1受体的激动剂,以及松弛的豚鼠气管,预先用ACh(100μM)进行了收缩。用5-HT1A选择性拮抗剂NAN-190(从10 nM到100μM)进行预处理可降低5-HT和5-CT的松弛作用,但仅在非常高的浓度下即可。最后,用一氧化氮合酶抑制剂L-硝基精氨酸甲酯(L-NAME,1 mM)和一氧化氮合成前体L-精氨酸(L-ARG,1 mM)进行了预处理。不会改变豚鼠气管中的5-HT和5-CT反应。总之,这项研究表明,豚鼠气管中的5-HT松弛活性是通过5-HT1受体激活而没有任何NO途径参与的。然而,需要进一步的研究来阐明5-HT1受体亚型与5-HT松弛作用有关。 [参考:21]

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