PnPP-19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidase

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dc.citation.issue9
dc.citation.volume173
dc.contributor.authorFreitas, A. C. N.
dc.contributor.authorPacheco, D. F.
dc.contributor.authorMachado, M. F. M. [UNIFESP]
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.authorDuarte, I. D. G.
dc.contributor.authorLima, M. E. de
dc.coverageHoboken
dc.date.accessioned2020-07-22T13:23:02Z
dc.date.available2020-07-22T13:23:02Z
dc.date.issued2016
dc.description.abstractBackground and PurposeThe synthetic peptide PnPP-19 has been studied as a new drug candidate to treat erectile dysfunction. However, PnTx2-6, the spider toxin from which the peptide was designed, induces hyperalgesia. Therefore, we intended to investigate the role of PnPP-19 in the nociceptive pathway. Experimental ApproachNociceptive thresholds were measured by paw pressure test. PnPP-19 was administered intraplantarly alone or with selective cannabinoid or opioid receptor antagonists. The hydrolysis of PnPP-19 by neutral endopeptidase (NEP) (EC 3.4.24.11), an enzyme that cleaves enkephalin, was monitored by HPLC and the cleavage sites were deduced by LC-MS. Inhibition by PnPP-19 and Leu-enkephalin of NEP enzyme activity was determined spectrofluorimetrically. Key ResultsPnPP-19 (5, 10 and 20g per paw) induced peripheral antinociception in rats. Specific antagonists of opioid receptors (clocinnamox), opioid receptors (naltrindole) and CB1 receptors (AM251) partly inhibited the antinociceptive effect of PnPP-19. Inhibition of fatty acid amide hydrolase by MAFP or of anandamide uptake by VDM11 enhanced PnPP-19-induced antinociception. NEP cleaved PnPP-19 only after a long incubation, and K-i values of 35.61.4 and 14.6 +/- 0.44 molL(-1)were determined for PnPP-19 and Leu-enkephalin respectively as inhibitors of NEP activity. Conclusions and ImplicationsAntinociception induced by PnPP-19 appears to involve the inhibition of NEP and activation of CB1, and opioid receptors. Our data provide a greater understanding of the antinociceptive effects of PnPP-19. This peptide could be useful as a new antinociceptive drug candidate.en
dc.description.affiliationUniv Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Farmacol, Belo Horizonte, MG, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPEMIG (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais)
dc.description.sponsorshipCAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
dc.description.sponsorshipCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
dc.description.sponsorshipINCTTOX (Instituto de Ciencia e Tecnologia em Toxinas)
dc.format.extent1491-1501
dc.identifierhttp://dx.doi.org/10.1111/bph.13448
dc.identifier.citationBritish Journal Of Pharmacology. Hoboken, v. 173, n. 9, p. 1491-1501, 2016.
dc.identifier.doi10.1111/bph.13448
dc.identifier.issn0007-1188
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56001
dc.identifier.wosWOS:000374008500007
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofBritish Journal Of Pharmacology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titlePnPP-19, a spider toxin peptide, induces peripheral antinociception through opioid and cannabinoid receptors and inhibition of neutral endopeptidaseen
dc.typeinfo:eu-repo/semantics/article
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