Inhibitory Effects On Human Eosinophil Chemotaxis In Vitro By Bay 41-2272, An Activator Of Nitric Oxide-independent Site Of Soluble Guanylate Cyclase.

dc.creatorThomazzi, Sara M
dc.creatorMoreira, Juliana
dc.creatorDe Nucci, Gilberto
dc.creatorAntunes, Edson
dc.date2005-Mar
dc.date2015-11-27T13:02:50Z
dc.date2015-11-27T13:02:50Z
dc.date.accessioned2018-03-29T01:02:11Z
dc.date.available2018-03-29T01:02:11Z
dc.identifierBiochemical Pharmacology. v. 69, n. 6, p. 875-82, 2005-Mar.
dc.identifier0006-2952
dc.identifier10.1016/j.bcp.2004.12.007
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/15748699
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/196609
dc.identifier15748699
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1296842
dc.descriptionThis study was designed to investigate the effects of the 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) on formyl-methionyl-leucyl-phenylalanine (fMLP; 10(-7)M)-induced human eosinophil chemotaxis, cyclic guanosine-3',5'-monophosphate (cGMP) and cyclic adenosine-3',5'-monophosphate (cAMP) levels. Human eosinophils were pretreated or not with 3-isobutyl-l-methyl-xanthine (IBMX; 500microM), and then exposed to BAY 41-2272 (0.1-10.0microM) for either short (10min) or prolonged (90min) time periods. Exposition of eosinophils with BAY 41-2272 for either 10min or 90min markedly inhibited the eosinophil chemotaxis, independently of IBMX pretreatment. Inhibition of fMLP-induced eosinophil chemotaxis by BAY 41-2272 (in absence of prior treatment with IBMX) was about of the same irrespective if cells were exposed for 10min or 90min with this compound. In IBMX-pretreated eosinophils, the inhibition of fMLP-induced chemotaxis by BAY 41-2272 in the 10-min exposure protocols was even higher in comparison with the 90-min protocols. Incubation of IBMX-treated eosinophils for 90min with BAY 41-2272 resulted in 2.0-2.5 times higher levels of cGMP and cAMP compared with the 10-min protocols. The BAY 41-2272-induced cGMP increases were abolished by pre-incubation of eosinophils with the soluble guanylate cyclase inhibitor 1H-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ). No eosinophil toxicity was observed in any experimental condition, according to 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Our findings show that inhibitory effects of fMLP-induced human eosinophil chemotaxis by BAY 41-2272 at short-term or prolonged exposition time are accompanied by significant elevations of cGMP and cAMP, but we could not detect a clear correlation between chemotaxis inhibition and elevation of cyclic nucleotide levels.
dc.description69
dc.description875-82
dc.languageeng
dc.relationBiochemical Pharmacology
dc.relationBiochem. Pharmacol.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChemotaxis, Leukocyte
dc.subjectDose-response Relationship, Drug
dc.subjectEosinophils
dc.subjectFemale
dc.subjectGuanylate Cyclase
dc.subjectHumans
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectNitric Oxide
dc.subjectPyrazoles
dc.subjectPyridines
dc.subjectReceptors, Cytoplasmic And Nuclear
dc.titleInhibitory Effects On Human Eosinophil Chemotaxis In Vitro By Bay 41-2272, An Activator Of Nitric Oxide-independent Site Of Soluble Guanylate Cyclase.
dc.typeArtículos de revistas


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