The Effects of Peptide and Lipid Endocannabinoids on Arthritic Pain at the Spinal Level

Petrovszki, Zita; Kovács, Gyula Z; Tömböly, Csaba; Benedek, György; Horváth, Gyöngyi

doi:10.1213/ane.0b013e31824c4eeb

Cited by 17 publications

(6 citation statements)

References 55 publications

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“…Systemic injection of hemopressin also produced marked antinociceptive potency in the acetic acid-induced visceral nociception model [1]. In contrast, hemopressin had no antinociceptive effects in the neuropathic spinal cord injury pain model and in the joint inflammation model at the spinal level [6,20]. Especially, in the formalin test, i.t.…”

Section: Discussionmentioning

confidence: 98%

“…The previous studies indicated that hemopressin was selectively bound to cannabinoid subtype-1 (CB 1 ) receptor with subnanomolar potency in brain, and acted as an endogenous antagonist or inverse agonist of CB 1 receptor [1,2]. The roles of hemopressin in the modulation of nociceptive signals have been evidenced in the previous studies [5,6]. Hemopressin was reported to attenuate carrageenan-induced mechanical allodynia at systemic, local, and spinal levels [1].…”

Section: Introductionmentioning

confidence: 98%

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Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice

Pan

Wang

et al. 2014

Neuroscience Letters

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice

Pan

Wang

et al. 2014

Neuroscience Letters

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“…These characteristics support the enzymatic function of EPHX1. 2-AG activity in stress, depression, and pain (37)(38)(39)(40). Furthermore, free AA is further metabolized by cyclooxygenases, lipoxygenases, and cytochrome P450s to biologically active eicosanoids that mediate infl ammation, vasodilation, vasoconstriction, cell growth, and migration.…”

Section: Downloaded Frommentioning

confidence: 99%

A novel activity of microsomal epoxide hydrolase: metabolism of the endocannabinoid 2-arachidonoylglycerol

Nithipatikom

Endsley

Pfeiffer

et al. 2014

Journal of Lipid Research

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including environmental chemicals and many therapeutic drugs. This enzymatic action converts lipophilic and sometimes reactive epoxides to more polar 1,2-diols. It also activates (pro)toxins and (pro)carcinogens ( 1, 2 ). In addition to xenobiotic metabolism, EPHX1 regulates endogenous steroid metabolism ( 3 ), bile acid transportation ( 4 ), and the vitamin K1 reductase complex that is responsible for vitamin K1 oxide reduction activity ( 5 ). While a number of diverse functions of EPHX1 have been demonstrated, only a few naturally endogenous substrates for EPHX1 have been characterized ( 3,(6)(7)(8).2-Arachidonoylglycerol (2-AG) is a highly abundant endogenous ligand for the cannabinoid receptor type 1 (CB1) ( 9-11 ). Through the activation of CB1, 2-AG plays a major role in a variety of physiological processes. The actions of 2-AG are tightly regulated by enzymatic hydrolysis, a major deactivation pathway. Monoacylglycerol lipase (MGL) ( 12, 13 ) and possibly FA amide hydrolase (FAAH) ( 14 ) are responsible for hydrolysis of 2-AG to free arachidonic acid (AA) and glycerol. Non-FAAH or non-MGL enzymes in porcine membranes ( 15 ) and mouse microglial cells ( 16 ) have been demonstrated to hydrolyze 2-AG. Recent studies discovered two integral membrane enzymes, ␣ / ␤ -hydrolase fold 6 and 12, that contributed to ‫ف‬ 4% and 9% of total 2-AG hydrolysis, respectively, in mouse brain membrane ( 17,18 ).The amino acid sequence of human EPHX1 indicates an epoxide hydrolase N terminus at the amino acids 50- Microsomal epoxide hydrolase (EPHX1, EC 3.3.2.9) is a xenobiotic metabolizing enzyme that is functionally associated with the cytochrome P450 family. The commonly known function of EPHX1 is to metabolize xenobiotics

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“…On the other hand, the analgesic effect of Hp is not conclusive, since Petrovszki et al (2012) showed that intrathecally administered hemopressin could not decrease hyperalgesia at the spinal level in carrageenan-induced mechanical allodynic model. In agreement with Petrovzki results, Hama and Sagen (2011) showed that central or systemic administration of Hp did not have antinociceptive actions in a rat model of neuropathic spinal cord injury pain.…”

Section: Hemopressin Peptides In Physiological Functionsmentioning

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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The Effects of Peptide and Lipid Endocannabinoids on Arthritic Pain at the Spinal Level

Cited by 17 publications

References 55 publications

Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice

Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice

A novel activity of microsomal epoxide hydrolase: metabolism of the endocannabinoid 2-arachidonoylglycerol

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

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