@article { , title = {The peptide PnPP-19, a spider toxin derivative, activates ?-opioid receptors and modulates calcium channels}, abstract = {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.}, doi = {10.3390/toxins10010043}, eissn = {2072-6651}, issue = {1}, journal = {Toxins}, pages = {1-12}, publicationstatus = {Published}, publisher = {MDPI}, url = {https://nottingham-repository.worktribe.com/output/3112148}, volume = {10}, year = {2018}, author = {Freitas, Ana C.N. and Peigneur, Steve and Macedo, Flávio H.P. and Menezes-Filho, José E. and Millns, Paul and Medeiros, Liciane F. and Arruda, Maria A. and Cruz, Jader and Holliday, Nicholas D. and Tytgat, Jan and Hathway, Gareth and de Lima, Maria E.} }