<i>S</i>  (+)-Ketamine Suppresses Desensitization of γ-Aminobutyric Acid Type B Receptor-mediated Signaling by Inhibition of the Interaction of γ-Aminobutyric Acid Type B Receptors with G Protein–coupled Receptor Kinase 4 or 5

Ando, Yumiko; Hojo, Mariko; Kanaide, Masato; Takada, Masafumi; Sudo, Yuka; Shiraishi, Seiji; Sumikawa, Koji; Uezono, Yasuhito

doi:10.1097/aln.0b013e318204e003

Cited by 13 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While a synergistic effect was not obtained, an additive combination may still be clinically useful. For example, tolerance and withdrawal following long-term baclofen could be suppressed with an adjuvant such as ketamine or [Ser 1 ]histogranin (Ando et al, 2011; Coffey et al, 2002; Heetla et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

Hama

Sagen

2012

European Journal of Pharmacology

View full text Add to dashboard Cite

Underlying below-level cutaneous hypersensitivity observed following spinal cord injury (SCI) is a concurrent loss of inhibition with an increase in excitation in the spinal dorsal horn. Thus, a dual pharmacological approach, increasing spinal γ-aminobutyrate (GABA) inhibition and decreasing N-methyl-D-aspartate (NMDA) receptor-mediated excitation, could be more beneficial than either approach alone. The current study evaluated the antinociceptive effects of lumbar intrathecal (i.t.) administration of GABA receptor agonists and NMDA receptor antagonists alone and in combination in rats with neuropathic SCI pain. Rats developed markedly decreased hind paw withdrawal thresholds following an acute thoracic spinal cord compression, indicative of below-level hypersensitivity. Separately, i.t. GABAA receptor agonist muscimol and GABAB receptor agonist baclofen demonstrated dose-dependent antinociception, whereas i.t. NMDA receptor antagonist ketamine and the endogenous peptide [Ser1]histogranin, a putative NMDA receptor antagonist, demonstrated no efficacy. The combination of baclofen and ketamine resulted in a supra-additive (synergistic) antinociception whereas the combinations with muscimol were merely additive. Intrathecal pretreatment with the GABAB receptor antagonist CGP 35348 prevented the antinociceptive effect of the baclofen and ketamine combination. The data indicate that blocking spinal NMDA receptors alone is not sufficient to ameliorate SCI hypersensitivity, whereas a combined approach, simultaneous activation of spinal GABAB receptors and NMDA receptors blockade with ketamine, leads to significant antinociception. By engaging diverse pain modulating systems at the spinal level, combination drug treatment may be a useful approach in treating neuropathic SCI pain.

show abstract

Section: Discussionmentioning

confidence: 99%

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

Hama

Sagen

2012

European Journal of Pharmacology

View full text Add to dashboard Cite

show abstract

“…It is not possible to perform chronic recordings during the first postnatal days because of brain and bone growth. Many anaesthetic agents shift the polarity of GABA and augment inhibition rendering the interpretation of results obtained in these conditions difficult (Desfeux et al, 2010; Ando et al, 2011; McNally et al, 2011). Acute un-anaesthetized recordings generate even more complications both because of pain and ethical issues but also due to the release of adrenaline and other stress agents that may shift the polarity of GABA actions.…”

Section: The Issue Of In Vivo Studies In Rodentsmentioning

confidence: 99%

Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!

Ben-Ari¹,

Woodin²,

Sernagor³

et al. 2012

Front. Cell. Neurosci.

140

125

View full text Add to dashboard Cite

During brain development, there is a progressive reduction of intracellular chloride associated with a shift in GABA polarity: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. This sequence has also been considerably reinforced recently with new data pointing to an evolutionary preserved rule. In a recent “Hypothesis and Theory Article,” the excitatory action of GABA in early brain development is suggested to be “an experimental artefact” (Bregestovski and Bernard, 2012). The authors suggest that the excitatory action of GABA is due to an inadequate/insufficient energy supply in glucose-perfused slices and/or to the damage produced by the slicing procedure. However, these observations have been repeatedly contradicted by many groups and are inconsistent with a large body of evidence including the fact that the developmental shift is neither restricted to slices nor to rodents. We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology.

show abstract

“…Because GRK4 and GRK5 compete with the G protein for binding at GABA B2 (Havlickova et al, 2002;Robbins et al, 2001), GRKs may induce desensitization by uncoupling the G protein from the receptor (Benke et al, 2012). A followup study showed that GRK4-and GRK5-induced desensitization in heterologous cells is partially suppressed in the presence of ketamine, an NMDA receptor antagonist (Ando et al, 2011). Ketamine was reported to inhibit the association of the GRKs with GABA B Rs, but the underlying mechanism was not revealed.…”

Section: Grk-induced Fast Desensitizationmentioning

confidence: 96%

Mechanisms of Fast Desensitization of GABAB Receptor-Gated Currents

Raveh

Tureček

Bettler

2015

Diversity and Functions of GABA Receptors: A Tribute to Hanns Möhler, Part B

View full text Add to dashboard Cite

S (+)-Ketamine Suppresses Desensitization of γ-Aminobutyric Acid Type B Receptor-mediated Signaling by Inhibition of the Interaction of γ-Aminobutyric Acid Type B Receptors with G Protein–coupled Receptor Kinase 4 or 5

Abstract: S(+)-Ketamine suppressed the desensitization of GABABR-mediated signaling at least in part through inhibition of formation of protein complexes of GB2R with GRK 4 or 5.

Cited by 13 publications

References 45 publications

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!

Mechanisms of Fast Desensitization of GABAB Receptor-Gated Currents

Contact Info

Product

Resources

About