Opioid Receptors and their Ligands

Janecka, Anna; Fichna, Jakub; Janecki, Tomasz

doi:10.2174/1568026043451618

Cited by 262 publications

(193 citation statements)

References 151 publications

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“…For more data on endomorphin analogs, please refer to the articles by Janecka et al (2004), Gentilucci and Tolomelli (2004), and Janecka and Kruszynski (2005).…”

Section: Structure-activity Relationship Studiesmentioning

confidence: 99%

The Endomorphin System and Its Evolving Neurophysiological Role

Fichna

Janecka²,

Costentin³

et al. 2007

Pharmacol Rev

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222

171

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“…For more data on endomorphin analogs, please refer to the articles by Janecka et al (2004), Gentilucci and Tolomelli (2004), and Janecka and Kruszynski (2005).…”

Section: Structure-activity Relationship Studiesmentioning

confidence: 99%

The Endomorphin System and Its Evolving Neurophysiological Role

Fichna

Janecka²,

Costentin³

et al. 2007

Pharmacol Rev

Self Cite

222

171

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“…Similarly, the pro-dynorphin-derived peptides, the dynorphins and neoendorphins, are generally localized to similar regions as the k-opioid receptor; however, it is likely that, in some regions, dynorphins may also activate the MOP. All of the opioid peptides have varying affinities for all three opioid receptors, and none are significantly selective for one receptor subtype (Mansour et al, 1995;Janecka et al, 2004). Finally, the precursor genes for endomorphin-1 (endo-1) and endomorphin-2 (endo-2) are still unknown, and therefore, these two ligands remain "putatively endogenous"; however, they are the most selective and potent opioid peptides for the MOP (Zadina et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Biased Agonism of Endogenous Opioid Peptides at theμ-Opioid Receptor

et al. 2015

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Biased agonism is having a major impact on modern drug discovery, and describes the ability of distinct G protein-coupled receptor (GPCR) ligands to activate different cell signaling pathways, and to result in different physiologic outcomes. To date, most studies of biased agonism have focused on synthetic molecules targeting various GPCRs; however, many of these receptors have multiple endogenous ligands, suggesting that "natural" bias may be an unappreciated feature of these GPCRs. The m-opioid receptor (MOP) is activated by numerous endogenous opioid peptides, remains an attractive therapeutic target for the treatment of pain, and exhibits biased agonism in response to synthetic opiates. The aim of this study was to rigorously assess the potential for biased agonism in the actions of endogenous opioids at the MOP in a common cellular background, and compare these to the effects of the agonist D-Ala2-N-MePhe4-Gly-ol enkephalin (DAMGO). We investigated activation of G proteins, inhibition of cAMP production, extracellular signal-regulated kinase 1 and 2 phosphorylation, b-arrestin 1/2 recruitment, and MOP trafficking, and applied a novel analytical method to quantify biased agonism. Although many endogenous opioids displayed signaling profiles similar to that of DAMGO, a-neoendorphin, Met-enkephalin-Arg-Phe, and the putatively endogenous peptide endomorphin-1 displayed particularly distinct bias profiles. These may represent examples of natural bias if it can be shown that they have different signaling properties and physiologic effects in vivo compared with other endogenous opioids. Understanding how endogenous opioids control physiologic processes through biased agonism can reveal vital information required to enable the design of biased opioids with improved pharmacological profiles and treat diseases involving dysfunction of the endogenous opioid system.

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“…26 The endogenous opioids are dynorphins, enkephalins, endorphins and nociceptin. Three large opioid receptor families, the μ-, κ, and δ-receptor subtypes, were cloned in 1990 and the nociceptin or orphanin FQ receptor (NOR), a fourth member of the opioid receptor subtype, was attached to the list in 1994 (Table 1).…”

Section: Opioid Receptor Physiologymentioning

confidence: 99%

The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

Özdemir

2017

Int J Basic Clin Pharmacol

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Continuous treatment with opioid analgesics, such as morphine, leads to the development of ant nociceptive tolerance in patients. Although a lot of information about antinociceptive, the pathophysiological mechanisms of tolerance to opioid analgesia are not yet completely understood. Proposed mechanisms for opioid analgesic tolerance comprise down-regulation of opioid receptors, reduction of sensitivity G-proteins, altered intracellular signalling pathway including nitric oxide, adenyl cyclase, and protein kinase C. Numerous physiological and behavioural studies have shown an interaction of the serotonergic system and opioid antinociception. The serotonin (5-HT) receptor system is a necessary component of the spinal and midbrain pain modulation circuit mediating opioid analgesia. Various types of serotonin receptors demonstrate different effects on morphine analgesia. Systemic administration of opioids rise 5-HT levels in the spinal cord dorsal horn and contribute to opioid analgesia in the normal state but reduce that in neuropathic pain via spinal 5-HT3 receptors. Spinal and supraspinal serotonergic neurons may also play a pathophysiological role in the development of morphine analgesic tolerance. Serotonin receptor subtypes show different effects on opioid tolerance. This review paper focus on the current understanding of the role of serotonin receptor systems in opioid analgesia and tolerance.

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Opioid Receptors and their Ligands

Cited by 262 publications

References 151 publications

The Endomorphin System and Its Evolving Neurophysiological Role

The Endomorphin System and Its Evolving Neurophysiological Role

Biased Agonism of Endogenous Opioid Peptides at theμ-Opioid Receptor

The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

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