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PnPP-19, un péptido de toxina araña, induce la antinocicepción periférica a través de los receptores opioides y cannabinoides y la inhibición de la en

REVISTA

Descripción: Investigacion del papel de PnPP-19 en la vía nociceptiva

TITULO FUENTE ORIGINAL:

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

AUTORES:

Freitas AC, Pacheco DF, Machado MF, Carmona AK, Duarte ID, de Lima ME

REVISTA ABREV.:

Br J Pharmacol

AÑO:

2016

REFERENCIA:

173(9):1491-501

DOI:

10.1111/bph.13448

RESUMEN ORIGINAL:

BACKGROUND AND PURPOSE:
The 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 APPROACH:
Nociceptive thresholds were measured by paw...
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BACKGROUND AND PURPOSE:
The 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 APPROACH:
Nociceptive 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 RESULTS:
PnPP-19 (5, 10 and 20 μg per paw) induced peripheral antinociception in rats. Specific antagonists of μ opioid receptors (clocinnamox), δ 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 Ki values of 35.6 ± 1.4 and 14.6 ± 0.44 μmol·L(-1) were determined for PnPP-19 and Leu-enkephalin respectively as inhibitors of NEP activity.

CONCLUSIONS AND IMPLICATIONS:
Antinociception induced by PnPP-19 appears to involve the inhibition of NEP and activation of CB1, μ and δ 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

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Enlace al pdf de acceso libre: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC[...]