The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels
AbstractThe 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
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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.
Freitas ACN, Peigneur S, Macedo FHP, Menezes-Filho JE, Millns P, Medeiros LF, Arruda MA, Cruz J, Holliday ND, Tytgat J, Hathway G, De Lima ME. The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels. Toxins. 2018; 10(1):43.Chicago/Turabian Style
Freitas, Ana C.N.; Peigneur, Steve; Macedo, Flávio H.P.; Menezes-Filho, José E.; Millns, Paul; Medeiros, Liciane F.; Arruda, Maria A.; Cruz, Jader; Holliday, Nicholas D.; Tytgat, Jan; Hathway, Gareth; De Lima, Maria E. 2018. "The Peptide PnPP-19, a Spider Toxin Derivative, Activates μ-Opioid Receptors and Modulates Calcium Channels." Toxins 10, no. 1: 43.
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