Spinal ERK activation via NO–cGMP pathway contributes to nociceptive behavior induced by morphine-3-glucuronide

Komatsu, Toshimitsu; Sakurada, Shinobu; Kohno, Kazuhiro; Shiohira, Hideo; Katsuyama, Soh; Sakurada, Chikai; Tsuzuki, Minoru; Sakurada, Tsukasa

doi:10.1016/j.bcp.2009.06.106

Cited by 21 publications

(17 citation statements)

References 53 publications

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“…Moreover, ERK 1/2 inhibitors can attenuate the analgesic effect evoked by morphine [29,30] and block the increased open arm-time after morphine withdrawal on EPM [31]. There is no data about the effect of obestatin on ERK 1/2 pathway in the central nervous system after in vivo treatment, but obestatin might exert its effect on mild morphine withdrawal and analgesia via regulation of ERK 1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5 μg/2 μl) was administrated once a day in all experiments. Furthermore, 0.2 mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20 mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120 min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.

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Section: Discussionmentioning

confidence: 99%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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“…Given the important role of spinal glial cells in neuropathic pain (Ji et al, 2013b;Zhang et al, 2012), these data support that the antinociceptive effect of HO-1 may, at least in part, be mediated through inhibition of glial activation in the spinal cord. We do not exclude the possibility that HO-1 may exert anti-nociceptive effect via modulation of neuronal nitric oxide synthase (NOS1) (Chu et al, 2005;Hervera et al, 2012) and cGMP (Komatsu et al, 2009;Nascimento and Branco, 2008) in spinal neurons.…”

Section: Ho-1 Induction Reduces Glial Activation In the Spinal Cordmentioning

confidence: 98%

Exogenous induction of HO-1 alleviates vincristine-induced neuropathic pain by reducing spinal glial activation in mice

Yan

Zhang

Zhu

et al. 2015

Neurobiology of Disease

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“…The influence of NO/cGMP/PKG signal pathway activation on RIRI is rarely seen in literatures. However, studies about cardiac IRI suggested that NO/cGMP/PKG signal transduction mechanism might be associated with activation of PKG and opening of ATP-sensitive K + channel in the cell membrane [31]; PKG as the downstream signaling protein of cGMP could activate ATP-sensitive K + channel. In summary, we speculated that curcumin may activate the downstream PKG-regulated ATP-sensitive K + channel through NO/cGMP/PKG signaling pathway to ultimately reduce the degree of IRI and induce the renal protection.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, research hotspots focus on energy metabolism disorder, reactive oxygen, signaling pathways, etc. There into, energy metabolism disorder is considered to be the initiation link of RIRI, while the signaling pathway of NO/cGMP/PKG, all which [NO, cGMP and PKG (cGMP-dependent protein kinase)] play important biological functions in a variety of histocytes, is considered as the key link to induce IRI [29-31]. PKG is an extensively existed serine/threonine kinase in eukaryocytes, while cGMP plays the role as the second messenger through the interaction between intracellular receptor proteins, in which the most key receptor of cGMP in the vascular smooth muscle cells is serine/threonine kinase (i.e., PKG) [32].…”

Section: Discussionmentioning

confidence: 99%

Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway

Liu

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue’s NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. Methods: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method. All groups’ β2-MG in urine in 24h, serum Cr and BUN were compared, and UAER were calculated. Nitric oxide synthase (NOS), cGMP-dependent protein kinase (PKG), Caspase-3 expression were all determined by western blot. Nitric oxide (NO), NOS and cGMP levels were also examined by using ELISA. All groups’ nephridial histomorphology and kidney tubules score were evaluated and compared. Results: β2-MG and UAER in urine, serum Cr and BUN, in renal tissue were all elevated in Model of RIRI, indicating the success of animal model of RIRI establishment, and above index in CUR + Model group were all lower than those in Model group. Furthermore, iNOS, NO, cGMP, PKG and Caspase-3 in renal tissue were all increased in Model of RIRI, indicating the NO signaling pathway was activated, which is one of the pathogenesis of RIRI, and above index in CUR + Model group were all lower than those in Model group, suggesting that inactivation of iNOS/NO/cGMP/PKG signaling pathway is one of the reasons that explain the protective effect of curcumin in RIRI. Conclusion: The activation of iNOS/NO/cGMP/PKG signaling pathway and the consequent promoted apoptosis of renal tubules are significantly involved in the pathogenesis of development of RIRI, and curcumin treatment could protect renal tubules against RIRI, at least partially, by suppressing the activated iNOS/NO/cGMP/PKG signaling pathway.

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Spinal ERK activation via NO–cGMP pathway contributes to nociceptive behavior induced by morphine-3-glucuronide

Cited by 21 publications

References 53 publications

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Exogenous induction of HO-1 alleviates vincristine-induced neuropathic pain by reducing spinal glial activation in mice

Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway

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