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  • 1.
    Carlsson, Jens
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Structure-guided discovery of adenosine receptor ligands2018In: Purinergic Signalling Purinergic Signalling, ISSN 1573-9538, E-ISSN 1573-9546, Vol. 14, no Suppl. 1, p. S51-S51Article in journal (Other academic)
  • 2. Chizhmakov, Igor
    et al.
    Kulyk, Vyacheslav
    Khasabova, Iryna
    Khasabov, Sergey
    Simone, Donald
    Bakalkin, Georgy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gordienko, Dmitri
    Verkhratsky, Alexei
    Krishtal, Oleg
    Molecular mechanism for opioid dichotomy: bidirectional effect of mu-opioid receptors on P2X(3) receptor currents in rat sensory neurones2015In: Purinergic Signalling Purinergic Signalling, ISSN 1573-9538, E-ISSN 1573-9546, Vol. 11, no 2, p. 171-181Article in journal (Refereed)
    Abstract [en]

    Here, we describe a molecular switch associated with opioid receptors-linked signalling cascades that provides a dual opioid control over P2X(3) purinoceptor in sensory neurones. Leu-enkephalin inhibited P2X(3)-mediated currents with IC50 similar to 10 nM in similar to 25 % of small nociceptive rat dorsal root ganglion (DRG) neurones. In contrast, in neurones pretreated with pertussis toxin leu-enkephalin produced stable and significant increase of P2X(3) currents. All effects of opioid were abolished by selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nonselective inhibitor naloxone, and by PLC inhibitor U73122. Thus, we discovered a dual link between purinoceptors and mu-opioid receptors: the latter exert both inhibitory (pertussis toxin-sensitive) and stimulatory (pertussis toxin-insensitive) actions on P2X(3) receptors through phospholipase C (PLC)-dependent pathways. This dual opioid control of P2X(3) receptors may provide a molecular explanation for dichotomy of opioid therapy. Pharmacological control of this newly identified facilitation/inhibition switch may open new perspectives for the adequate medical use of opioids, the most powerful pain-killing agents known today.

  • 3. Ellegaard, Maria
    et al.
    Karlsson, Magnus
    Lorentzon, Mattias
    Ohlsson, Claes
    Mellstrom, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Schwarz, Peter
    Jorgensen, Niklas Rye
    Single-nucleotide polymorphism in the P2Y(2) receptor gene is associated with bone mineral density in a cohort of Swedish elderly men2014In: Purinergic Signalling Purinergic Signalling, ISSN 1573-9538, E-ISSN 1573-9546, Vol. 10, no 4, p. 751-751, article id B015Article in journal (Other academic)
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