Wolf M, Benko R, Undi S, Dekany A, Illenyi L, Papp A, Varga G, Zapf I, Bartho L
Department of Pharmacology and Pharmacotherapy University Medical School of Pecs, Pecs, Hungary.
Methods Find Exp Clin Pharmacol. 2009 Jul-Aug;31(6):359-66. doi: 10.1358/mf.2009.31.6.1393630.
The in vitro pharmacology of inosine (Ino), a putative anti-inflammatory compound, has been investigated in smooth muscle preparations, with emphasis on its possible interaction with known inflammatory mediators, as well as capsaicin, an inducer of "neurogenic inflammation". The highest concentration of Ino routinely studied was 1 mM, since 10 mM nonspecifically inhibited many types of smooth muscle motor responses. In the guinea pig isolated ileum or trachea, Ino (1 mM) failed to influence the excitatory effect of capsaicin. The nitric oxide (NO)-mediated relaxant effect of capsaicin in the human colonic circular muscle was not influenced by Ino. Ino only weakly reduced the contractile effect of histamine on the guinea pig ileum. Substance P-mediated nonadrenergic, noncholinergic (NANC) contractions evoked by electrical stimulation in the guinea pig ileum were inhibited by half by Ino (1 mM). Ino showed no or only a weak inhibitory effect on NANC relaxation of the rat ileum. Arachidonic acid- or leukotriene D(4)-induced contractions of the guinea pig ileum were only moderately inhibited by Ino. Collectively, these results indicate that Ino (up to 1 mM) shows no major antagonist activity at histamine H(1) receptors, leukotriene CysLT(1) receptors, the transient receptor potential channel TRPV1 or tachykinin NK(1) or NK(2) receptors, or cyclooxygenase-inhibitory activity. Therefore, its anti-inflammatory activity is probably not associated with these mechanisms. The in vitro methods used in this study are capable of detecting a wide range of biological effects and hence may be recommended as a screening procedure for potential drugs or natural products.
肌苷（Ino）是一种假定的抗炎化合物，其体外药理学已在平滑肌制剂中进行了研究，重点是它与已知炎症介质以及辣椒素（一种“神经源性炎症”诱导剂）的可能相互作用。常规研究的Ino最高浓度为1 mM，因为10 mM会非特异性抑制多种类型的平滑肌运动反应。在豚鼠离体回肠或气管中，Ino（1 mM）未能影响辣椒素的兴奋作用。辣椒素在人结肠环行肌中由一氧化氮（NO）介导的舒张作用不受Ino影响。Ino仅微弱降低组胺对豚鼠回肠的收缩作用。电刺激在豚鼠回肠中诱发的P物质介导的非肾上腺素能、非胆碱能（NANC）收缩被Ino（1 mM）抑制了一半。Ino对大鼠回肠的NANC舒张没有或仅有微弱的抑制作用。花生四烯酸或白三烯D4诱导的豚鼠回肠收缩仅被Ino适度抑制。总体而言，这些结果表明，Ino（高达1 mM）在组胺H1受体、白三烯CysLT1受体、瞬时受体电位通道TRPV1或速激肽NK1或NK2受体上没有主要的拮抗活性，也没有环氧化酶抑制活性。因此，其抗炎活性可能与这些机制无关。本研究中使用的体外方法能够检测广泛的生物学效应，因此可推荐作为潜在药物或天然产物的筛选程序。
