Time-Dependent Effects of In Vivo Pertussis Toxin on Morphine Analgesia and G-Proteins in Mice

Shah, Sukrut; Breivogel, C. S.; Selly, D.; Munirathinam, G; Childers, Steven R.; Yoburn, Byron C.

doi:10.1016/s0091-3057(96)00234-1

Cited by 10 publications

(3 citation statements)

References 16 publications

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“…However, the extent to which these changes are attributable to PT alone, or the combined treatments used to induce EAE, remains un-documented. However, other studies have shown that PT alone evokes changes in BBB function leading to increased protein infiltration into the brain (~15 days; [169]), or disruption of G-protein function (~40 days; [170]) following PT administration. In the present study, repeated injections of PT during the second and third weeks of CPZ-feeding resulted in proteoform changes after 5 or 12 weeks indicating that PT injections alone have long-term effects at least on the brain proteome.…”

Section: Discussionmentioning

confidence: 99%

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Sen

Almuslehi

Gyengési

et al. 2019

Cells

106

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Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

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Section: Discussionmentioning

confidence: 99%

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Sen

Almuslehi

Gyengési

et al. 2019

Cells

106

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“…The antinociceptive effect of morphine is mediated by a G protein subtype sensitive to PTX, a selective inhibitor of Gi/Go (Hoehn et al, 1988;Chang et al, 1991;Shah et al, 1997). However, little is known about the G protein mediating the effect of oxycodone.…”

Section: Antinociceptive Effects Of Morphine and Oxycodone By Icv mentioning

confidence: 99%

G protein‐gated inwardly rectifying potassium (K_IR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

Nakamura

Fujita

Ono

et al. 2013

British J Pharmacology

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Background and Purpose Oxycodone and morphine are μ‐opioid receptor agonists prescribed to control moderate‐to‐severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein‐gated inwardly rectifying potassium (KIR3 also known as GIRK) channels in their antinociceptive effects. Experimental Approach Opioid‐induced antinociceptive effects were assessed in mice, using the tail‐flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of KIR3.1 channels with tertiapin‐Q (30 pmol per mouse, i.c.v. and i.t.) and KIR3.1‐specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin‐Q administration in the mouse femur bone cancer and neuropathic pain models. Key Results The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by KIR3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by KIR3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin‐Q. Conclusion and Implications These results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone.

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“…A very similar pertussis toxin sensitive mechanism has been well documented in morphine antinociception. [157][158][159][160] Analyzed together with our in vitro studies, 130,132,133 it is possible that the antinociception produced by Phyllanthus active principles involves multiple mechanisms of action, such as interaction with noxious neuropeptides, for example tachykinin, released from sensory neurones, or with excitatory amino acid, such as glutamate or aspartate, recently reported to modulate neurogenic pain. [148][149][150] However, the confirmation of this hypothesis awaits further studies.…”

Section: A N T I N O C I C E P T I O N O F T H E E X T R a C T A N D mentioning

confidence: 99%

A review of the plants of the genusPhyllanthus: Their chemistry, pharmacology, and therapeutic potential

et al. 1998

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Time-Dependent Effects of In Vivo Pertussis Toxin on Morphine Analgesia and G-Proteins in Mice

Cited by 10 publications

References 16 publications

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

G protein‐gated inwardly rectifying potassium (K_IR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

A review of the plants of the genusPhyllanthus: Their chemistry, pharmacology, and therapeutic potential

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Time-Dependent Effects of In Vivo Pertussis Toxin on Morphine Analgesia and G-Proteins in Mice

Cited by 10 publications

References 16 publications

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

G protein‐gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

A review of the plants of the genusPhyllanthus: Their chemistry, pharmacology, and therapeutic potential

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Product

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G protein‐gated inwardly rectifying potassium (K_IR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites