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Toxins 2018, 10(1), 43; doi:10.3390/toxins10010043

The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels

Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Toxicology and Pharmacology, KU Leuven, 3000 Leuven, Belgium
Arthritis Research UK Pain Centre, School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Cell Signaling Research Group, School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Farmanguinhos, Fiocruz, Brazilian Ministry of Health, Rio de Janeiro 22775-903, Brazil
Author to whom correspondence should be addressed.
Received: 22 December 2017 / Revised: 11 January 2018 / Accepted: 12 January 2018 / Published: 15 January 2018
(This article belongs to the Special Issue Toxins in Drug Discovery and Pharmacology)
View Full-Text   |   Download PDF [1902 KB, uploaded 15 January 2018]   |  


The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors. Furthermore, we also studied the modulation of calcium influx driven by PnPP-19 in dorsal root ganglion neurons, and analyzed whether this modulation was opioid-mediated. PnPP-19 selectively activates μ-opioid receptors inducing indirectly inhibition of calcium channels and hereby impairing calcium influx in dorsal root ganglion (DRG) neurons. Interestingly, notwithstanding the activation of opioid receptors, PnPP-19 does not induce β-arrestin2 recruitment. PnPP-19 is the first spider toxin derivative that, among opioid receptors, selectively activates μ-opioid receptors. The lack of β-arrestin2 recruitment highlights its potential for the design of new improved opioid agonists. View Full-Text
Keywords: Phoneutria nigriventer; opioid receptor; spider toxin; antinociception Phoneutria nigriventer; opioid receptor; spider toxin; antinociception

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Freitas, A.C.N.; Peigneur, S.; Macedo, F.H.P.; Menezes-Filho, J.E.; Millns, P.; Medeiros, L.F.; Arruda, M.A.; Cruz, J.; Holliday, N.D.; Tytgat, J.; Hathway, G.; de Lima, M.E. The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels. Toxins 2018, 10, 43.

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