Soluble guanylyl cyclase activators increase the expression of tolerance to morphine analgesic effect

Durmuş, Nedim; Bağcıvan, İhsan; Özdemir, Ercan; Altun, Ahmet; Gürsoy, Sinan

doi:10.4149/bll_2014_066

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…For example, there is substantial evidence for nitrosyl factors playing roles in 1) opioid receptor (OR) signaling processes ( Pol, 2007 ; Toda et al, 2009a ; Toda et al, 2009b ; Rodríguez-Muñoz and Garzón, 2013 ), and 2) opioid effects on a) vascular function and reactivity ( Sahin et al, 2005 ; Kaye et al, 2006 ), b) pain processing ( Pelligrino, et al, 1996 ; Maegawa and Tonussi, 2003 ; Cury et al, 2011 ; Hervera et al, 2011 ; Mehanna et al, 2018 ; Ortiz et al, 2020 ), c) vision ( Someya et al, 2017 ), and d) inflammatory-immunoregulatory processes ( Bilfinger, et al, 1998 ; Jan et al, 2011 ). Additionally, nitrosyl factors are involved in opioid-induced catalepsy ( Erkent et al, 2006 ), tolerance to opioids ( Kissin et al, 2000 ; Ozdemir et al, 2011 ; Durmus et al, 2014 ), and fentanyl pre-conditioning ( Lu et al, 2014 ). Nonetheless, only a few studies have sought evidence as to potential roles for nitrosyl factors in the ventilatory depressant effects of opioids.…”

Section: Introductionmentioning

confidence: 99%

S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats

Getsy

Baby²,

Gruber³

et al. 2022

Front. Pharmacol.

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Endogenous and exogenously administered S-nitrosothiols modulate the activities of central and peripheral systems that control breathing. We have unpublished data showing that the deleterious effects of morphine on arterial blood-gas chemistry (i.e., pH, pCO2, pO2, and sO2) and Alveolar-arterial gradient (i.e., index of gas exchange) were markedly diminished in anesthetized Sprague Dawley rats that received a continuous intravenous infusion of the endogenous S-nitrosothiol, S-nitroso-L-cysteine. The present study extends these findings by showing that unanesthetized adult male Sprague Dawley rats receiving an intravenous infusion of S-nitroso-L-cysteine (100 or 200 nmol/kg/min) markedly diminished the ability of intravenous injections of the potent synthetic opioid, fentanyl (10, 25, and 50 μg/kg), to depress the frequency of breathing, tidal volume, and minute ventilation. Our study also found that the ability of intravenously injected fentanyl (10, 25, and 50 μg/kg) to disturb eupneic breathing, which was measured as a marked increase of the non-eupneic breathing index, was substantially reduced in unanesthetized rats receiving intravenous infusions of S-nitroso-L-cysteine (100 or 200 nmol/kg/min). In contrast, the deleterious effects of fentanyl (10, 25, and 50 μg/kg) on frequency of breathing, tidal volume, minute ventilation and non-eupneic breathing index were fully expressed in rats receiving continuous infusions (200 nmol/kg/min) of the parent amino acid, L-cysteine, or the D-isomer, namely, S-nitroso-D-cysteine. In addition, the antinociceptive actions of the above doses of fentanyl as monitored by the tail-flick latency assay, were enhanced by S-nitroso-L-cysteine, but not L-cysteine or S-nitroso-D-cysteine. Taken together, these findings add to existing knowledge that S-nitroso-L-cysteine stereoselectively modulates the detrimental effects of opioids on breathing, and opens the door for mechanistic studies designed to establish whether the pharmacological actions of S-nitroso-L-cysteine involve signaling processes that include 1) the activation of plasma membrane ion channels and receptors, 2) selective intracellular entry of S-nitroso-L-cysteine, and/or 3) S-nitrosylation events. Whether alterations in the bioavailability and bioactivity of endogenous S-nitroso-L-cysteine is a key factor in determining the potency/efficacy of fentanyl on breathing is an intriguing question.

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Section: Introductionmentioning

confidence: 99%

S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats

Getsy

Baby²,

Gruber³

et al. 2022

Front. Pharmacol.

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“…These agents include: nitric oxide (NO) synthase inhibitors, calcium channel blockers, substance P receptor (NK-1) antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists, cyclooxygenase (COX) inhibitors, antagonists of the NMDA (N-methyl-D-aspartate) receptor, cholecystokinin (CCK) receptor antagonists, and 5-HT receptor agonists. [8][9][10][11][12][13][14][15][16][17] Serotonergic neurons are involved in the formation of spinal cord pain. 18 Stimulation of serotonergic neurons decreases the pain responses through a descending inhibitory pathway in the spinal cord dorsal horn.…”

Section: Introductionmentioning

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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Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?

Gledhill

Babey

2021

Cell Mol Neurobiol

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Soluble guanylyl cyclase activators increase the expression of tolerance to morphine analgesic effect

Cited by 4 publications

References 25 publications

S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats

S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats

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

Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?

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