Role of l -arginine/nitric oxide/cyclic GMP/K ATP channel signaling pathway and opioid receptors in the antinociceptive effect of rutin in mice.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-09-02 DOI:10.1097/FBP.0000000000000792
Sadaf Fayazzadeh, Sajad Fakhri, Fatemeh Abbaszadeh, Mohammad Hosein Farzaei
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Abstract

The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20 min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.

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l-精氨酸/一氧化氮/环GMP/KATP通道信号通路和阿片受体在芦丁对小鼠抗痛觉作用中的作用
众所周知,l-精氨酸(l-Arg)/一氧化氮/环GMP/钾通道(KATP)通路和阿片受体在痛觉和各种化合物的抗痛觉作用中起着关键作用。虽然有证据表明芦丁的镇痛作用可能涉及一氧化氮的调节,但芦丁与 l-Arg/一氧化氮/环 GMP/KATP 通路在疼痛调节方面的直接联系还需要进一步研究。我们使用福尔马林试验研究了芦丁对雄性 NMRI 小鼠的抗痛觉作用。为了研究 l-Arg/一氧化氮/环 GMP/KATP 通路和阿片受体的作用,对小鼠腹腔内进行了不同物质的预处理。这些物质包括 l-Arg(一氧化氮前体)、S-亚硝基-N-乙酰青霉胺(SNAP,一氧化氮供体)、N(γ)-硝基-精氨酸甲酯(L-NAME,一氧化氮合酶抑制剂)、西地那非(磷酸二酯酶抑制剂)、格列本脲(KATP 通道阻断剂)和纳洛酮(阿片受体拮抗剂)。所有预处理均在芦丁最有效剂量给药前 20 分钟进行。根据我们的研究发现,芦丁具有剂量依赖性的抗痛觉作用。在初始和继发阶段,给予 SNAP 均可增强芦丁的镇痛效果。此外,L-NAME、纳洛酮和格列本脲可降低芦丁在初级和次级阶段的镇痛效果。总之,芦丁作为一种具有镇痛特性的类黄酮具有重要价值,其镇痛作用是通过一氧化氮/环GMP/KATP通道直接介导的。
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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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