uu.seUppsala University Publications
Change search
Refine search result
1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Akerman, Karl E. O.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Nasman, Johnny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Lund, Per-Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Shariatmadari, Ramin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Kukkonen, Jyrki P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Endogenous extracellular purine nucleotides redirect alpha2-adrenoceptor signaling1998In: FEBS Lett., Vol. 430, 209- p.Article in journal (Refereed)
  • 2.
    Gandasi, Nikhil R.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Yin, Peng
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Riz, Michela
    Univ Padua, Dept Informat Engn, Padua, Italy..
    Chibalina, Margarita V
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Cortese, Giuliana
    Univ Padua, Dept Stat Sci, Padua, Italy..
    Lund, Per-Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Matveev, Victor
    New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA..
    Rorsman, Patrik
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Sherman, Arthur
    NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA..
    Pedersen, Morten G
    Univ Padua, Dept Informat Engn, Padua, Italy..
    Barg, Sebastian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ca2+ channel clustering with insulin-containing granules is disturbed in type 2 diabetes2017In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 127, no 6, 2353-2364 p.Article in journal (Refereed)
    Abstract [en]

    Loss of first-phase insulin secretion is an early sign of developing type 2 diabetes (T2D). Ca2+ entry through voltage-gated L-type Ca2+ channels triggers exocytosis of insulin-containing granules in pancreatic β cells and is required for the postprandial spike in insulin secretion. Using high-resolution microscopy, we have identified a subset of docked insulin granules in human β cells and rat-derived clonal insulin 1 (INS1) cells for which localized Ca2+ influx triggers exocytosis with high probability and minimal latency. This immediately releasable pool (IRP) of granules, identified both structurally and functionally, was absent in β cells from human T2D donors and in INS1 cells cultured in fatty acids that mimic the diabetic state. Upon arrival at the plasma membrane, IRP granules slowly associated with 15 to 20 L-type channels. We determined that recruitment depended on a direct interaction with the synaptic protein Munc13, because expression of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2 domain all disrupted L-type channel clustering at granules and ablated fast exocytosis. Thus, rapid insulin secretion requires Munc13-mediated recruitment of L-type Ca2+ channels in close proximity to insulin granules. Loss of this organization underlies disturbed insulin secretion kinetics in T2D.

  • 3. Gustafsson, Amanda Jabin
    et al.
    Ingelman-Sundberg, Hanna
    Dzabic, Mensur
    Awasum, Justina
    Nguyen, Khanh Hoa
    Östenson, Claes-Göran
    Pierro, Cristina
    Tedeschi, Patrizia
    Woolcott, Orison
    Chiounan, Shiue
    Lund, Per-Eric
    Larsson, Olof
    Islam, M. Shahidul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells2005In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 19, no 2, 301-303 p.Article in journal (Refereed)
    Abstract [en]

    There is little information available concerning the link between the ryanodine (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura-2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7-dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was abolished by omission of extracellular Ca(2+) and by SKF 96365. In the presence of SKF 96365, MBED produced a transient increase of [Ca(2+)]i, which was abolished by thapsigargin. Activation of RY receptors caused Ca(2+) entry even when the ER Ca(2+) pool was depleted by thapsigargin. The [Ca(2+)]i plateau was not inhibited by nimodipine or ruthenium red, but was inhibited by membrane depolarization, La(3+), Gd(3+), niflumic acid, and 2-aminoethoxydiphenyl borate, agents that inhibit the transient receptor potential channels. The [Ca(2+)]i spikes were inhibited by nimodipine and ryanodine, indicating that they were due to Ca(2+) influx through the voltage-gated Ca(2+) channels and Ca(2+)-induced Ca(2+) release (CICR). Activation of RY receptors depolarized membrane potential as measured by patch clamp. Thus, activation of RY receptors leads to coherent changes in Ca(2+) signaling, which includes activation of TRP-like channels, membrane depolarization, activation of the voltage-gated Ca(2+) channels and CICR.

  • 4.
    Lund, Per-Eric
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Shariatmadari, Ramin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Uustare, Ain
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Detheux, M
    Parmentier, M
    Kukkonen, JP
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Akerman, Karl-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    The orexin OX(1) receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C*2000In: J Biol Chem, Vol. 275, 30806- p.Article in journal (Refereed)
  • 5. Macsari, Istvan
    et al.
    Besidski, Yeygeni
    Csjernyik, Gabor
    Nilsson, Linda I.
    Sandberg, Lars
    Yngve, Ulrika
    Ahlin, Kristofer
    Bueters, Tjerk
    Eriksson, Anders B.
    Lund, Per-Eric
    Venyike, Elisabet
    Oerther, Sandra
    Blakeman, Karin Hygge
    Luo, Lei
    Arvidsson, Per I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models2012In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 15, 6866-6880 p.Article in journal (Refereed)
    Abstract [en]

    The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

  • 6. Macsari, Istvan
    et al.
    Sandberg, Lars
    Besidski, Yevgeni
    Gravenfors, Ylva
    Ginman, Tobias
    Bylund, Johan
    Bueters, Tjerk
    Eriksson, Anders B.
    Lund, Per-Eric
    Venyike, Elisabet
    Arvidsson, Per I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Phenyl isoxazole voltage-gated sodium channel blockers: structure and activity relationship2011In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 21, no 13, 3871-3876 p.Article in journal (Refereed)
    Abstract [en]

    Blocking of certain sodium channels is considered to be an attractive mechanism to treat chronic pain conditions. Phenyl isoxazole carbamate 1 was identified as a potent and selective Na(V)1.7 blocker. Structural analogues of 1, both carbamates, ureas and amides, were proven to be useful in establishing the structure-activity relationship and improving ADME related properties. Amide 24 showed a good overall in vitro profile, that translated well to rat in vivo PK.

  • 7.
    Marshall, Misty
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lund, Per-Eric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Barg, Sebastian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Molecular Mechanisms of V-SNARE Function in Secretory Granule Exocytosis2017In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 112, no 3, 395A-395A p.Article in journal (Other academic)
1 - 7 of 7
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf