Abstract
BackgroundSome peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. In this study, we characterized the antinociceptive effect of the peptide PnPP-19 on the central nervous system and investigated the possible involvement of opioid and cannabinoid systems in its action mechanism.MethodsNociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. All drugs were administered by the intracerebroventricular route.ResultsPnPP-19 induced central antinociception in mice in the doses of 0.5 and 1 μg. The non-selective opioid receptor antagonist naloxone (2.5 and 5 μg), μ-opioid receptor antagonist clocinnamox (2 and 4 μg), δ-opioid receptor antagonist naltrindole (6 and 12 μg) and CB1 receptor antagonist AM251 (2 and 4 μg) partially inhibited the antinociceptive effect of PnPP-19 (1 μg). Additionally, the anandamide amidase inhibitor MAFP (0.2 μg), the anandamide uptake inhibitor VDM11 (4 μg) and the aminopeptidase inhibitor bestatin (20 μg) significantly enhanced the antinociception induced by a low dose of PnPP-19 (0.5 μg). In contrast, the κ-opioid receptor antagonist nor-binaltorphimine (10 μg and 20 μg) and the CB2 receptor antagonist AM630 (2 and 4 μg) do not appear to be involved in this effect.ConclusionsPnPP-19-induced central antinociception involves the activation of CB1 cannabinoid, μ- and δ-opioid receptors. Mobilization of endogenous opioids and cannabinoids might be required for the activation of those receptors, since inhibitors of endogenous substances potentiate the effect of PnPP-19. Our results contribute to elucidating the action of the peptide PnPP-19 in the antinociceptive pathway.
Highlights
Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment
PnPP-19 is a synthetic peptide that contains 19 amino acid residues [1]. It represents a part of the primary structure of the native toxin PnTx2-6, known as δctenitoxin-Pn2a [2], which was isolated from the venom of the spider Phoneutria nigriventer [3]
We have shown that PnPP-19 induces antinociception in the peripheral nervous system [17]. We suggested that this effect is attributable to an inhibition of the neutral endopeptidase, which may lead to an increase of enkephalin levels and may cause activation of both μ- and δ-opioid receptors
Summary
Some peptides purified from the venom of the spider Phoneutria nigriventer have been identified as potential sources of drugs for pain treatment. Our group has demonstrated the involvement of endogenous da Fonseca Pacheco et al Journal of Venomous Animals and Toxins including Tropical Diseases (2016) 22:34 opioids and cannabinoids in the antinociceptive action of several substances [9, 10]. Receptors for both drugs are coupled to similar intracellular signaling mechanisms and the interaction between cannabinoid and opioid systems in the nociceptive pathway has been the focus of much attention [9, 11,12,13,14,15]. Opioid peptides may be involved in the action mechanism of other toxins, toxins from other arthropods, such as the spider Phoneutria nigriventer
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