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

dc.creatorOlsen, Priscilla C.
dc.creatorCoelho, Luciana P.
dc.creatorCosta, Jorge C. S. da
dc.creatorCordeiro, Renato S. B.
dc.creatorSilva, Patrícia M. R.
dc.creatorMartins, Marco A.
dc.date2017-04-11T12:31:19Z
dc.date2017-04-11T12:31:19Z
dc.date2012
dc.date.accessioned2023-09-26T22:34:29Z
dc.date.available2023-09-26T22:34:29Z
dc.identifierOLSEN, Priscilla C. et al. 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, v.680, p.102-107, 2012.
dc.identifier0014-2999
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/18364
dc.identifier10.1016/j.ejphar.2012.01.040
dc.identifier1879-0712)
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8880586
dc.descriptionopen access
dc.descriptionInhalation 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 (0.1–1 mM) 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 (100 μM), but it was clearly sensitive to 9-(tetrahydro- 2-furyl) adenine (SQ22,536, 100 μM), an adenylate cyclase inhibitor. JMF2-1 (300 and 600 μM) also dosedependently 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 both systems. JMF2-1 induced apoptosis of anti-CD3 activated T cells in a mechanism sensitive to zIETD, indicating that JMF2-1 mediates caspase-8-dependent apoptosis. Furthermore, forskolin also inhibited anti-CD3 induced T cell proliferation and survival. Our results suggest that JMF2-1 inhibits respiratory smooth muscle contraction as well as T cell proliferation and survival through enhancement of intracellular cAMP levels. These findings may help to explain the anti-inflammatory and antispasmodic effects of JMF2-1 observed in previous studies.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectAsma
dc.subjectCélula T
dc.subjectCélula do músculo liso das vias aéreas
dc.subjectcAMP
dc.subjectT cell
dc.subjectAirway smooth muscle cell
dc.subjectAsthma
dc.subjectJMF2-1
dc.titleTwo for one: Cyclic AMP mediates the anti-inflammatory and anti-spasmodic properties of the non-anesthetic lidocaine analog JMF2-1
dc.typeArticle


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