Interest
- Research on heart failure, cellular signal transduction and development of new pharmacological targets for HFrEF and HFpEF.
Teaching
- Medical students: Pharmacology in module 3-6
- Courses: MF9250 – Methods in Cardiac Research
Administrative duties
Background
Tags:
FRET,
GPCR,
natriuretic peptide,
cAMP,
cGMP,
Receptor,
Hart Failure,
Biosensor
Publications
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Andressen, Kjetil Wessel; Ulsund, Andrea Hembre; Krobert, Kurt Allen; Lohse, Martin J.; Bünemann, Moritz & Levy, Finn Olav
(2017).
Related GPCRs couple differently to Gs: preassociation between G protein and 5-HT7 serotonin receptor reveals movement of Gαs upon receptor activation.
The FASEB Journal.
ISSN 0892-6638.
32(2),
p. 1059–1069.
doi:
10.1096/fj.201700486R.
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Moltzau, Lise Roman; Meier, Silja; Andressen, Kjetil Wessel & Levy, Finn Olav
(2017).
Compartmentation of Natriuretic Peptide Signalling in Cardiac Myocytes: Effects on Cardiac Contractility and Hypertrophy.
In Nikolaev, Viacheslav & Zaccolo, Manuela (Ed.),
Microdomains in the Cardiovascular System..
Springer.
ISSN 978-3-319-54578-3.
p. 245–271.
doi:
10.1007/978-3-319-54579-0_12.
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Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila; Frimurer, Thomas; Schwartz, Thue W. & Levy, Finn Olav
[Show all 7 contributors for this article]
(2015).
Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1.
ACS Chemical Neuroscience.
ISSN 1948-7193.
6(7),
p. 1206–1218.
doi:
10.1021/cn500339p.
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Olberg, Dag Erlend; Hausner, Sven H.; Bauer, Nadine; Klaveness, Jo; Indrevoll, Bård & Andressen, Kjetil Wessel
[Show all 10 contributors for this article]
(2015).
Radiosynthesis of high affinity fluorine-18 labeled
GnRH peptide analogues: in vitro studies and
in vivo assessment of brain uptake in rats.
MedChemComm.
ISSN 2040-2503.
6,
p. 708–714.
doi:
10.1039/c4md00486h.
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Olberg, Dag Erlend; Andressen, Kjetil Wessel; Levy, Finn Olav; Klaveness, Jo; Haraldsen, Ira Hebold & Sutcliffe, Julie L.
(2014).
Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression.
Bioorganic & Medicinal Chemistry Letters.
ISSN 0960-894X.
24(7),
p. 1846–1850.
doi:
10.1016/j.bmcl.2014.02.002.
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Brudeli, Bjarne; Andressen, Kjetil Wessel; Moltzau, Lise Roman; Nilsen, Nils Olav; Levy, Finn Olav & Klaveness, Jo
(2013).
Acidic biphenyl derivatives: Synthesis and biological activity of a new series of potent 5-HT4 receptor antagonists.
Bioorganic & Medicinal Chemistry.
ISSN 0968-0896.
21(22),
p. 7134–7145.
doi:
10.1016/j.bmc.2013.09.004.
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Brudeli, Bjarne; Moltzau, Lise Roman; Andressen, Kjetil Wessel; Krobert, Kurt Allen; Klaveness, Jo & Levy, Finn Olav
(2010).
Synthesis and pharmacological properties of novel hydrophilic 5-HT4 receptor antagonists.
Bioorganic & Medicinal Chemistry.
ISSN 0968-0896.
18(24),
p. 8600–8613.
doi:
10.1016/j.bmc.2010.10.011.
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Ngai, Jacob; Iversen, Trond Methi; Andressen, Kjetil Wessel; Levy, Finn Olav; Torgersen, Knut Martin & Vang, Torkel
[Show all 8 contributors for this article]
(2008).
The heterotrimeric G-protein α-subunit Gαq regulates TCR-mediated immune responses through an Lck-dependent pathway.
European Journal of Immunology.
ISSN 0014-2980.
38(11),
p. 3208–3218.
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Vinge, Leif Erik; Andressen, Kjetil Wessel; Attramadal, Toril; Andersen, Geir Øystein; Ahmed, Muhammad Shakil & Peppel, K
[Show all 12 contributors for this article]
(2007).
Substrate specificities of G protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function.
Molecular Pharmacology.
ISSN 0026-895X.
72,
p. 582–591.
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Andressen, Kjetil Wessel; Norum, Jens Henrik; Levy, Finn Olav & Krobert, Kurt Allen
(2006).
Activation of adenylyl cyclase by endogenous G(s)-coupled receptors in human embryonic kidney 293 cells is attenuated by 5-HT7 receptor expression.
Molecular Pharmacology.
ISSN 0026-895X.
69,
p. 207–215.
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Krobert, Kurt Allen; Andressen, Kjetil Wessel & Levy, Finn Olav
(2006).
Heterologous desensitization is evoked by both agonist and antagonist stimulation of the human 5-HT7 serotonin receptor.
European Journal of Pharmacology.
ISSN 0014-2999.
532,
p. 1–10.
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Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Molenaar, P.; Birkeland, Jon Arne & Andressen, Kjetil Wessel
[Show all 12 contributors for this article]
(2005).
Rationale for treatment of heart failure by blockade of ventricular serotonin receptors appearing in heart failure,
Proceedings of the 25th European Section Meeting, International Society for Heart Research, Tromsø, Norway, June 21-25, 2005.
Medimond.
ISSN 88-7587-164-7.
p. 7–12.
Show summary
Serotonin (5-hydroxytryptamine, 5-HT) enhances contractility and causes arrhythmias through human atrial 5-HT4 receptors. We recently found that porcine and human as well as failing rat cardiac ventricle also responds to serotonin through 5-HT4 receptors which, like beta-adrenoceptors, are coupled via the Gs protein to increased cAMP formation. In rats with 6-week post-infarction congestive heart failure (CHF), the maximal inotropic effect of serotonin was comparable in size with that of isoproterenol. Given the similar signalling systems utilised by the two receptors and that blockade of beta-adrenoceptors is beneficial in CHF, we propose that blockade of 5-HT4 receptors may also be beneficial in CHF.
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Qvigstad, Eirik; Brattelid, Trond; Sjaastad, Ivar; Andressen, Kjetil Wessel; Krobert, Kurt Allen & Birkeland, Jon Arne
[Show all 11 contributors for this article]
(2005).
Appearance of a ventricular 5-HT4 receptor-mediated inotropic response to serotonin in heart failure.
Cardiovascular Research (CVR).
ISSN 0008-6363.
65.
Show summary
BACKGROUND: Current pharmacological treatment of congestive heart failure (CHF) addresses changes in neurohumoral stimulation or cardiac responsiveness to such stimulation. Yet, undiscovered neurohumoral changes, adaptive or maladaptive, may occur in CHF and suggest novel pharmacological treatment. Serotonin [5-hydroxytryptamine (5-HT)] enhances contractility and causes arrhythmias through 5-HT(4) receptors in human atrium and ventricle but not through rat ventricular 5-HT(4) receptors. OBJECTIVE: We investigated whether CHF could induce ventricular responsiveness to serotonin. METHODS: Postinfarction CHF was induced in male Wistar rats by coronary artery ligation. Contractility was measured in left ventricular papillary muscles 6 weeks after infarction. Messenger RNA was quantified by RT-PCR and cAMP by RIA. RESULTS: Serotonin caused positive inotropic (-logEC(50)=7.5) and lusitropic effects in CHF but not Sham papillary muscles. The inotropic effect of 10 muM serotonin in CHF (31.3+/-2.2%) was of similar size as the effect of 10 muM isoproterenol (34.0+/-1.7%). The effects of serotonin were antagonised by GR113808 (0.5-5 nM), consistent with mediation through 5-HT(4) receptors. This was further supported by positive inotropic effects of the 5-HT(4)-selective partial agonist RS67506. Carbachol blunted the serotonin responses and serotonin increased ventricular and cardiomyocyte cAMP, consistent with coupling to G(s) and adenylyl cyclase. Quantitative RT-PCR revealed fourfold increased 5-HT(4(b)) mRNA expression in CHF vs. Sham ventricles. CONCLUSION: Functional ventricular 5-HT(4) receptors are induced by myocardial infarction and CHF of the rat heart. We propose that they are a model for ventricular 5-HT(4) receptors of human failing heart and may play a pathophysiological role in heart failure.
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Brattelid, Trond; Kvingedal, Ane Marit; Krobert, Kurt Allen; Andressen, Kjetil Wessel; Bach, Trond & Hystad, Marit Elise
[Show all 8 contributors for this article]
(2004).
Cloning, pharmacological characterisation and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i).
Naunyn-Schmiedeberg's Archives of Pharmacology.
ISSN 0028-1298.
369(6),
p. 616–628.
Show summary
5-HT4 receptor pre-mRNA is alternatively spliced in human (h) tissue to produce several splice variants, called 5-HT4(a) to 5-HT4(h) and 5-HT4(n). Polymerase chain reaction (PCR) with primers designed to amplify both 5-HT4(a) and 5-HT4(b) amplified three additional bands in different tissues, two representing different mRNA species both encoding 5-HT4(g) and one representing mRNA for a novel splice variant named 5-HT4(i), cloned from testis and pancreas respectively. Primary and nested PCR detected both 5-HT4(g) and 5-HT4(i) in multiple tissues. Whereas 5-HT4(i), was found in all cardiovascular tissues analysed, 5-HT4(g) was mainly present in atria. However, quantitative RT-PCR indicated 5-HT4(g) expression also in cardiac ventricle. The pharmacological profiles and ability to activate adenylyl cyclase (AC) were compared between four recombinant h5-HT4 splice variants (a, b, g and i) expressed transiently and stably in HEK293 cells. Displacement of [(3)H]GR113808 with ten ligands revealed identical pharmacological profiles (affinity rank order: GR125487, SB207710, GR113808>SB203186>serotonin, cisapride, tropisetron>renzapride, 5-MeOT>5-CT). In transiently transfected HEK293 cells cisapride was a partial agonist compared to serotonin at 5-HT4(b), 5-HT4(g) and 5-HT4(i) receptors. In membranes from HEK293 cells stably expressing 5-HT4(g) (3,000 fmol/mg protein) or 5-HT4(i) (500 fmol/mg protein), serotonin and 5-MeOT were full agonists while cisapride was full agonist at 5-HT4(g) and partial agonist at 5-HT4(i), probably due to different receptor expression levels. At both 5-HT4(g) and 5-HT4(i), the behaviour of 5-HT4 receptor antagonists was dependent on receptor level. At high receptor levels, tropisetron and SB207710 and to a variable extent SB203186 and GR113808 displayed some partial agonist activity, whereas GR125487 and SB207266 reduced the AC activity below basal, indicating both receptors to be constitutively active. We conclude that the novel 5-HT4(i) receptor splice variant is pharmacologically indistinguishable from other 5-HT4 splice variants and that the 5-HT4(i) C-terminal tail does not influence coupling to AC.
View all works in Cristin
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Dugstad, K.; Ulsund, Andrea Hembre; Aronsen, Jan Magnus; Sjaastad, Ivar; Zaccolo, Manuela & Levy, Finn Olav
[Show all 7 contributors for this article]
(2014).
Unraveling tight spatial regulation of 5-HT4 receptor-mediated inotropic effects using targeted FRET-based cAMP sensors.
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Dugstad, Kari Sandanger; Andressen, Kjetil Wessel; Aronsen, Jan Magnus; Sjaastad, Ivar; Zaccolo, Manuela & Levy, Finn Olav
(2012).
Compartmented production and degradation of cAMP by beta-adrenergic, prostanoid and 5-HT4 receptors in CHF, visualized by FRET-based cAMP sensors.
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Andressen, Kjetil Wessel; Dugstad, KS; Aronsen, Jan Magnus; Sjaastad, Ivar; Zaccolo, Manuela & Levy, Finn Olav
(2011).
Unraveling tight spatiotemporal regulation of cAMP-mediated inotropic effects using targeted FRET-based cAMP sensors.
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Andressen, Kjetil Wessel; Norum, Jens Henrik; Levy, Finn Olav & Krobert, Kurt Allen
(2006).
Activation of adenylyl cyclase in HEK293 cells by endogenous G(s)-coupled receptors is attenuated by 5-HT7 receptor expression.
Journal of Pharmacological Sciences (JPS).
ISSN 1347-8613.
101,
p. 128–128.
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View all works in Cristin
Published
Aug. 23, 2012 12:14 PM
- Last modified
June 7, 2023 8:53 AM