In vitro pharmacology of inosine, with special reference to possible interactions with capsaicin-sensitive mechanisms and inflammatory mediators

M. Wolf, R. Benko, S. Undi, A. Dekany, L. Illenyi, A. Papp, G. Varga, I. Zapf, Lorand Bartho

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 D4-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 H1 receptors, leukotriene CysLT1 receptors, the transient receptor potential channel TRPV1 or tachykinin NK1 or NK2 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.

Original languageEnglish
Pages (from-to)359-366
Number of pages8
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume31
Issue number6
DOIs
Publication statusPublished - Dec 18 2009

Keywords

  • Anti-inflammatory
  • Inflammatory mediators
  • Inosine
  • Neurotransmitters
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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