ArticleBritish journal of pharmacology2014
PI3Kγ integrates cAMP and Akt signalling of the μ-opioid receptor.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- Neuroprotective and Anti-inflammatory Effects of Rubiscolin-6 Analogs with Proline Surrogates in Position 2.Neurochemical research · 2024Article
- Bidirectional Regulation of Opioid and Chemokine Function.Frontiers in immunology · 2020Review
- Adenosine, Via AHypertension (Dallas, Tex. : 1979) · 2020Article
- Effect of Wnt signaling pathway on pathogenesis and intervention of neuropathic pain.Experimental and therapeutic medicine · 2018Article
- Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway.Inflammation · 2016Article
- Adenosine Attenuates Human Coronary Artery Smooth Muscle Cell Proliferation by Inhibiting Multiple Signaling Pathways That Converge on Cyclin D.Hypertension (Dallas, Tex. : 1979) · 2015Article
- Downregulation of PI3Kcb utilizing adenovirus-mediated transfer of siRNA attenuates bone cancer pain.International journal of clinical and experimental pathology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe μ-opioid receptor has been characterized as the main mediator of opioid signalling in neuronal cells. Opioid-induced pain suppression was originally proposed to be mediated by μ-opioid receptor-induced inhibitory effects on cAMP, which is known to mediate inflammatory hypernociception. Recent investigations revealed PI3Kγ and Akt (PKB) as additional elements of μ-opioid receptor signalling. Hence, we investigated the interaction between pronociceptive cAMP and antinociceptive PI3K/Akt signalling pathways. EXPERIMENTAL APPROACH: The human neuroblastoma cell line SK-N-LO and primary dorsal root ganglia (DRG) cells from mice were used to elucidate mediators of μ-opioid receptor signalling. In both cellular systems cAMP was manipulated by stimulation of adenylate cyclase and consequent effects on PI3K/Akt signalling were analysed. KEY
resultsMorphine stimulated Akt phosphorylation on Ser(473) and Thr(308) in a dose- and time-dependent manner indicating a functional μ-opioid receptor/Akt signalling pathway in μ-SK-N-LO cells. This effect of morphine was suppressed by the μ-opioid receptor inhibitor, naloxone, Pertussis toxin, an inhibitor of Gi heterotrimeric G-proteins, and the pan PI3K inhibitor wortmannin. cAMP-elevating agents also suppressed μ-opioid receptor-dependent stimulation of PI3Kγ lipid kinase and Akt activities in SK-N-LO cells and DRG. CONCLUSIONS AND IMPLICATIONS: The data unveil a hitherto unknown interaction of pronociceptive cAMP and antinociceptive PI3K/Akt signalling pathways in neuronal cells. PI3Kγ was identified as a mediator of the inhibitory action of cAMP on Akt in SK-N-LO cells and DRG. The data indicate that PI3Kγ has a critical role in cAMP-mediated inflammatory hypernociception and analgesic signalling via μ-opioid receptors and PI3K/Akt in neuronal cells.
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