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The peptide PnPP-19, a spider toxin derivative, activates ?-opioid receptors and modulates calcium channels


Ana C.N. Freitas

Steve Peigneur



Paul Millns

Liciane F. Medeiros

Maria A. Arruda

Jader Cruz

Jan Tytgat

Maria E. de Lima


The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin ?-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, ? and ? 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 ?-, ?- and/or ?-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 ?-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 ?-arrestin2 recruitment. PnPP-19 is the first spider toxin derivative that, among opioid receptors, selectively activates ?-opioid receptors. The lack of ?-arrestin2 recruitment highlights its potential for the design of new improved opioid agonists.


Freitas, A. C., Peigneur, S., Macedo, F. H., Menezes-Filho, J. E., Millns, P., Medeiros, L. F., …de Lima, M. E. (2018). The peptide PnPP-19, a spider toxin derivative, activates μ-opioid receptors and modulates calcium channels. Toxins, 10(1), 1-12.

Journal Article Type Article
Acceptance Date Jan 12, 2018
Online Publication Date Jan 15, 2018
Publication Date Jan 15, 2018
Deposit Date May 27, 2020
Publicly Available Date May 27, 2020
Journal Toxins
Electronic ISSN 2072-6651
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 43
Pages 1-12
Public URL
Publisher URL