Two for one: cyclic AMP mediates the anti-inflammatory and anti-spasmodic properties of the non-anesthetic lidocaine analog JMF2-1

European Journal of Pharmacology
Priscilla C OlsenMarco Aurélio Martins

Abstract

Inhalation of JMF2-1, an analog of lidocaine with reduced anesthetic activity, prevents airway contraction and lung inflammation in experimental asthma models. We sought to test if the JMF2-1 effects are a consequence of increased intracellular cAMP levels in asthma cell targets, such as smooth muscle cells and T cells. Functional effect of JMF2-1 on carbachol-induced contraction of intact or epithelial-denuded rat trachea was assessed in conventional organ baths. cAMP was quantified by radioimmunoassay in cultured guinea pig tracheal smooth muscle cells, as well as lymph node cells from BALB/c mice, exposed to JMF2-1. We found that JMF2-1 (0.1-1mM) concentration-dependently inhibited epithelium-intact tracheal ring contraction induced by carbachol challenge. The antispasmodic effect remained unaltered following epithelium removal or pretreatment with NG-nitro-L-arginine methyl ester (100μM), but it was clearly sensitive to 9-(tetrahydro-2-furyl) adenine (SQ22,536, 100μM), an adenylate cyclase inhibitor. JMF2-1 (300 and 600μM) also dose-dependently increased cAMP intracellular levels of both cultured airway smooth muscle cells and T lymphocytes. This effect was consistently abrogated by SQ22,536 and reproduced by forskolin in b...Continue Reading

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Citations

Jul 16, 2014·International Journal of Critical Illness and Injury Science·Stanislaw P StawickiThomas J Papadimos
Oct 4, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Geeta NegiShyam S Sharma
May 30, 2015·The Journal of Endocrinology·Daniella B R InsuelaVinicius F Carvalho

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