Effects of Mlx-8, a phospholipase A2 from Brazilian coralsnake Micrurus lemniscatus venom, on muscarinic acetylcholine receptors in rat hippocampus

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dc.contributorLaboratório de Farmacologiapt_BR
dc.contributorLaboratório de Bioquímica e Biofísicapt_BR
dc.contributorLaboratório de Fisiopatologiapt_BR
dc.contributor.authorSantos, Roberta Tancredi Francesco dospt_BR
dc.contributor.authorSilva, Marcelo Florêncio Passospt_BR
dc.contributor.authorMarques-Porto, Rafaelpt_BR
dc.contributor.authorLebrun, Ivopt_BR
dc.contributor.authorGonçalves, Luis Roberto de Camargopt_BR
dc.contributor.authorBatista, Isabel de Fátima Correiapt_BR
dc.contributor.authorSandoval, Maria Regina Lopespt_BR
dc.contributor.authorAbdalla, Fernando Maurício Francispt_BR
dc.date.accessioned2020-07-09T21:26:34Z-
dc.date.available2020-07-09T21:26:34Z-
dc.date.issued2020-
dc.identifier.citationSantos RTF, Silva MFP, Marques-Porto R, Lebrun I, Gonçalves LRC, Batista IFC, et al. Effects of Mlx-8, a phospholipase A2 from Brazilian coralsnake Micrurus lemniscatus venom, on muscarinic acetylcholine receptors in rat hippocampus. J. Venom. Anim. Toxins Incl. Trop. Dis.. 2020 Jan;26:e20190041. doi:10.1590/1678-9199-jvatitd-2019-0041.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2944-
dc.description.abstractBackground: Here, we described the presence of a neurotoxin with phospholipase A2 activity isolated from Micrurus lemniscatus venom (Mlx-8) with affinity for muscarinic acetylcholine receptors (mAChRs). Methods: The purification, molecular mass determination, partial amino acid sequencing, phospholipase A2 activity determination, inhibition of the binding of the selective muscarinic ligand [3H]QNB and inhibition of the total [3H]inositol phosphate accumulation in rat hippocampus of the Mlx-8 were determined. Results: Thirty-one fractions were collected from HPLC chromatography, and the Mlx-8 toxin was used in this work. The molecular mass of Mlx-8 is 13.628 Da. Edman degradation yielded the following sequence: NLYQFKNMIQCTNTRSWL-DFADYG-CYCGRGGSGT. The Mlx-8 had phospholipase A2 enzymatic activity. The pKi values were determined for Mlx-8 toxin and the M1 selective muscarinic antagonist pirenzepine in hippocampus membranes via [3H]QNB competition binding assays. The pKi values obtained from the analysis of Mlx-8 and pirenzepine displacement curves were 7.32 ± 0.15, n = 4 and 5.84 ± 0.18, n = 4, respectively. These results indicate that Mlx-8 has affinity for mAChRs. There was no effect on the inhibition ability of the [3H]QNB binding in hippocampus membranes when 1 µM Mlx-8 was incubated with 200 µM DEDA, an inhibitor of phospholipase A2. This suggests that the inhibition of the phospholipase A2 activity of the venom did not alter its ability to bind to displace [3H]QNB binding. In addition, the Mlx-8 toxin caused a blockade of 43.31 ± 8.86%, n = 3 and 97.42 ± 2.02%, n = 3 for 0.1 and 1 µM Mlx-8, respectively, on the total [3H]inositol phosphate content induced by 10 µM carbachol. This suggests that Mlx-8 inhibits the intracellular signaling pathway linked to activation of mAChRs in hippocampus. Conclusion: The results of the present work show, for the first time, that muscarinic receptors are also affected by the Mlx-8 toxin, a muscarinic ligand with phospholipase A2 characteristics, obtained from the venom of the Elapidae snake Micrurus lemniscatus, since this toxin was able to compete with muscarinic ligand [3H]QNB in hippocampus of rats. In addition, Mlx-8 also blocked the accumulation of total [3H]inositol phosphate induced by muscarinic agonist carbachol. Thus, Mlx-8 may be a new pharmacological tool for examining muscarinic cholinergic function.pt_BR
dc.format.extente20190041pt_BR
dc.languageengpt_BR
dc.relation.ispartofJournal of Venomous Animals and Toxins Including Tropical Diseasespt_BR
dc.rightsOpen Accesspt_BR
dc.titleEffects of Mlx-8, a phospholipase A2 from Brazilian coralsnake Micrurus lemniscatus venom, on muscarinic acetylcholine receptors in rat hippocampuspt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1590/1678-9199-jvatitd-2019-0041pt_BR
dc.identifier.urlhttps://doi.org/10.1590/1678-9199-jvatitd-2019-0041pt_BR
dc.identifier.citationvolume26pt_BR
dc.subject.keywordMuscarinic receptorspt_BR
dc.subject.keywordHippocampuspt_BR
dc.subject.keywordMicrurus lemniscatuspt_BR
dc.subject.keywordInositol phosphatept_BR
dc.subject.keywordPhopholipase A2pt_BR
dc.relation.ispartofabbreviatedJ. Venom. Anim. Toxins Incl. Trop. Dis.pt_BR
dc.identifier.citationabntv. 16, e20190041, jan. 2020pt_BR
dc.identifier.citationvancouver2020 Jan;26:e20190041pt_BR
dc.contributor.butantanSantos, Roberta Tancredi Francesco dos|:Aluno|:Laboratório de Farmacologia|:PrimeiroAutorpt_BR
dc.contributor.butantanLebrun, Ivo|:Pesquisador:Docente Permanente PPGTOX|:Laboratório de Bioquímica e Biofísica|:pt_BR
dc.contributor.butantanGonçalves, Luis Roberto de Camargo|:Pesquisador:Docente Colaborador PPGTOX|:Laboratório de Fisiopatologia|:pt_BR
dc.contributor.butantanAbdalla, Fernando Maurício Francis|:Pesquisador:Docente Colaborador PPGTOX|:Laboratório de Farmacologia|:Autor de correspondênciapt_BR
dc.contributor.butantanSilva, Marcelo Florêncio Passos|:Aluno|:Laboratório de Farmacologia|:pt_BR
dc.contributor.butantanMarques-Porto, Rafael|:Técnico|:Laboratório de Bioquímica e Biofísica|:pt_BR
dc.contributor.butantanBatista, Isabel de Fátima Correia|:Pesquisador|:Laboratório de Bioquímica e Biofísica|:pt_BR
dc.contributor.butantanSandoval, Maria Regina Lopes|:Pesquisador|:Laboratório de Farmacologia|:pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
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item.grantfulltextembargo_29990101-
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