Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice

Pan, Jia-Xin; Wang, Zilong; Li, Ning; Zhang, Nan; Wang, Pei; Tang, Hong-hai; Zhang, Ting; Yu, Hongping; Zhang, Run; Zheng, Ting; Fang, Quan; Wang, Rui

doi:10.1016/j.ejphar.2015.10.016

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…NPFF has recently been published to modulate cannabinoid-induced antinociception after i.c.v. administration of mouse VD-hemopressin(α) (an extended analog of Hp(1-9)) in naive and VD-hemopressin(α) tolerant mice (Pan et al, 2015). In naive mice, i.c.v.…”

Section: Discussionmentioning

confidence: 99%

Investigation of receptor binding and functional characteristics of hemopressin(1–7)

et al. 2016

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The orally active, α-hemoglobin derived hemopressin (PVNFKFLSH, Hp(1-9)) and its truncated (PVNFKFL, Hp(1-7) and PVNFKF, Hp(1-6)) and extended ((R)VDPVNFKFLSH, VD-Hp(1-9) and RVD-Hp(1-9)) derivatives have been postulated to be the endogenous peptide ligands of the cannabinoid receptor type 1 (CB1). In an attempt to create a versatile peptidic research tool for the direct study of the CB1 receptor-peptide ligand interactions, Hp(1-7) was radiolabeled and in vitro characterized in rat and CB1 knockout mouse brain membrane homogenates. In saturation and competition radioligand binding studies, [(3)H]Hp(1-7) labeled membrane receptors with high densities and displayed specific binding to a receptor protein, but seemingly not to the cannabinoid type 1, in comparison the results with the prototypic JWH-018, AM251, rimonabant, Hp(1-9) and RVD-Hp(1-9) (pepcan 12) ligands in both rat brain and CB1 knockout mouse brain homogenates. Furthermore, functional [(35)S]GTP γS binding studies revealed that Hp(1-7) and Hp(1-9) only weakly activated G-proteins in both brain membrane homogenates. Based on our findings and the latest literature data, we assume that the Hp(1-7) peptide fragment may be an allosteric ligand or indirect regulator of the endocannabinoid system rather than an endogenous ligand of the CB1 receptor.

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Section: Discussionmentioning

confidence: 99%

Investigation of receptor binding and functional characteristics of hemopressin(1–7)

et al. 2016

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“…Hemopressin peptides were shown to regulate the function of other non-canonical cannabinoid receptors in a diverse of physiological functions (Li et al, 2014;Sampaio et al, 2015, Fogaça et al, 2015Szlaviz et al, 2015;Pan et al, 2015;Zheng et al, 2018;Leone et al, 2018) (Table 2). In an animal model of anxiety, the i. c.v administration of Hp induced anxiogenic-like effects that were blocked by the addition of a TRPV1 antagonist (Fogaça et al, 2015;).…”

Section: Modulation Of Cannabinoid Receptors By Peptide Cannabinoidsmentioning

confidence: 99%

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

et al. 2020

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Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, endocannabinoids also bind to other groups of receptors. Furthermore, another group of lipids are considered to be endocannabinoids, such as the fatty acid ethanolamides, the fatty acid primary amides and the monoacylglycerol related molecules. Recently, it has been shown that the hemopressin peptide family, derived from α and β chains of hemoglobins, is a new family of cannabinoids. Some studies indicate that hemopressin peptides are expressed in the central nervous system and peripheral tissues and act as ligands of these receptors, thus suggesting that they play a physiological role. In this review, we examine new evidence on lipid endocannabinoids, cannabinoid receptors and the modulation of their signaling pathways. We focus our discussion on the current knowledge of the pharmacological effects, the biosynthesis of the peptide cannabinoids and the new insights on the activation and modulation of cannabinoid receptors by these peptides. The novel peptide compounds derived from hemoglobin chains and their non-classical activation of cannabinoid receptors are only starting to be uncovered. It will be exciting to follow the ensuing discoveries, not only in reference to what is already known of the classical lipid endocannabinoids revealing more complex aspects of endocannabinoid system, but also as to its possibilities as a future therapeutic tool.

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“…Hp(1-9) also showed low potency (EC 50 = 29 ± Figure 18 and Table 7). The agonist control compound DAMGO exhibited low potency (EC 50 = 177 ± 21 nM) and significant stimulation (E max = 167 ± 20%) of [ 35 with the potency obtained in rat brain membrane homogenate. However, Hp(1-7) displayed very similar stimulatory effects in both wild type rat and CB1 knockout mouse brain homogenates (E max = 112 ± 12 and 117 ± 18%).…”

Section: Preparation and Receptor Binding Properties Of [ 3 H]hemoprementioning

confidence: 88%

“…33,34 In addition, central administration of VD-Hpα resulted in tolerance to antinociception and stimulated food consumption in a CB1-dependent manner. 34,35 The signaling characteristics and regulation of receptor endocytosis by the Nterminally extended peptide fragments were found to be distinct, in part, from those of the classical cannabinoid agonists. 31 Recently, it was described that the nonapeptide hemopressin might rather be a hot acidic extraction artifact and it is not present endogenously.…”

Section: Hemopressins (Pepcans) the Putative Peptide Endocannabinoidsmentioning

confidence: 99%

“…and the bivalent compounds 10-12 retain their ability to stimulate the receptor-associated G-proteins, the synthetic compounds were subjected to ligand-stimulated [35 S]GTPγS binding assays in rat brain membrane homogenate. It is important to mention that this preparation abundantly contains both MOR and CB receptors, therefore it is an appropriate model to investigate the capability of the MOR agonist oxycodone and its derivatives, and also the cannabinoid agonist JWH-018 and its derivatives.…”

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confidence: 99%

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Targeting the cannabinoid and mu opioid receptors with heterodimerized and allosteric ligands

Dvorácskó

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Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice

Cited by 8 publications

References 41 publications

Investigation of receptor binding and functional characteristics of hemopressin(1–7)

Investigation of receptor binding and functional characteristics of hemopressin(1–7)

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

Targeting the cannabinoid and mu opioid receptors with heterodimerized and allosteric ligands

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