| 1. |
- Bergdahl, Anders, et al.
(författare)
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Neuropeptide Y potentiates noradrenaline-induced contraction through the neuropeptide Y Y1 receptor
- 1996
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 316:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate which neuropeptide Y receptor subtype is responsible for the neuropeptide Y-induced potentiation of the noradrenaline-evoked contraction in human omental arteries we used antisense oligodeoxynucleotide (Antisense), the new selective neuropeptide Y Y1 receptor antagonist, BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginine-amide} and the reverse transcriptase-polymerase chain reaction (RT-PCR). Neuropeptide Y significantly potentiated the noradrenaline-induced contraction in non-incubated vessels (pEC50 6.4 +/- 0.2 vs. 5.9 +/- 0.2) and in vessels incubated with 1 microM Sense oligodeoxynucleotide (Sense) (pEC50 6.0 +/- 0.1 vs. 5.6 +/- 0.2). In vessels incubated with 1 microM Antisense the potentiating effect of neuropeptide Y was completely abolished. BIBP3226 (1 microM) inhibited the neuropeptide Y-induced potentiation in human omental arteries (pEC50 5.8 +/- 0.3 vs. 6.4 +/- 0.2). Finally, messenger RNA for the neuropeptide Y Y1 receptor was detected using RT-PCR. On the basis of our results we conclude that the neuropeptide Y-induced potentiation of the noradrenaline-induced contraction is mediated by the neuropeptide Y Y1 receptor.
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| 2. |
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| 3. |
- Malmlof, Torun, et al.
(författare)
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Deuterium substitutions in the L-DOPA molecule improve its anti-akinetic potency without increasing dyskinesias
- 2010
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 225:2, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of Parkinson's disease is complicated by a high incidence of L-DOPA-induced dyskinesias (LID). Strategies to prevent the development of LID aim at providing more stable dopaminergic stimulation. We have previously shown that deuterium substitutions in the L-DOPA molecule (D3-L-DOPA) yield dopamine that appears more resistant to enzymatic breakdown. We here investigated the effects of D3-L-DOPA on motor performance and development of dyskinesias in a rodent model of Parkinson's disease. Through acute experiments, monitoring rotational behavior, dose effect curves were established for D3-L-DOPA and L-DOPA. The equipotent dose of D3-L-DOPA was estimated to be 60% of L-DOPA. Subsequently, animals were treated with either the equipotent dose of D3-L-DOPA (5 mg/kg), the equivalent dose of D3-L-DOPA (8 mg/kg), L-DOPA (8 mg/kg) or vehicle. The equivalent dose of D3-L-DOPA produced superior anti-akinetic effects compared to L-DOPA in the cylinder test (p<0.05), whereas the equipotent dose of D3-L-DOPA produced an anti-akinetic effect similar to L-DOPA. Dyskinesias developed to the same degree in the groups treated with equivalent doses of D3-L-DOPA and L-DOPA. The equipotent dose of D3-L-DOPA induced fewer dyskinesias than L-DOPA (p<0.05). In conclusion, our study provides evidence for improved potency and reduced side-effects of L-DOPA by deuterium substitutions in the molecule. These results are of clinical interest since the occurrence of LID is related to the total L-DOPA dose administered. D3-L-DOPA may thus represent a novel strategy to reduce the total dose requirement and yet achieve an effective control of parkinsonian symptoms. (C) 2010 Elsevier Inc. All rights reserved.
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| 4. |
- Nilsson-Bergdahl, Torun
(författare)
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Neuropeptide Y - aspects of vasomotorresponses and receptor characterization
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract The aims of the present thesis were to examine neuropeptide Y (NPY) responses in different human and guinea pig vascular beds and in cultured human vascular smooth muscle cells (VSMC) and to characterize, with different NPY agonists and the specific NPY Y1 receptor antagonist (BIBP3226), the NPY receptors involved. NPY-induced strong and potent contractions in human cerebral and subcutaneous arteries and in guinea pig basilar arteries. The contractions were shown to be mediated solely by the NPY Y1 receptor. In human omental and guinea pig mesenteric arteries, NPY failed to induce contraction, instead a strong, NPY-induced, NPY Y1 receptor-mediated, potentiation of the noradrenaline (NA) -induced contraction was seen. Treatment with antisense oligodeoxynucleotides against the NPY Y1 receptor mRNA abolished the potentiation. The acetylcholine (ACh) -induced dilatation of guinea pig basilar arteries was attenuated by NPY. The receptor involved seemed to be the NPY Y2 receptor. In 50% of the human subcutaneous arteries studied, NPY, apart from contraction, also induced a NPY Y1 receptor-mediated and nitric oxide (NO) dependent vasodilatation. With reverse transcriptase-polymerase chain reaction (RT-PCR) mRNA encoding the human NPY Y1 receptor was detected in human cerebral, subcutaneous and omental arteries and in endothelial cells from human umbilical veins. In cultured VSMC from human subcutaneous arteries, NPY stimulated DNA synthesis and potentiated the NA-induced mitogenesis. Both responses appeared to be induced by the NPY Y1 receptor. Administration of NPY and NA, in-vivo, into the human brachial artery reduced forearm blood flow and increased forearm vascular resistance. The opposite effects were seen after infusion of ATP. The responses were equal in potency and strength in hypertensive and normotensive subjects.
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| 5. |
- Nilsson, Torun, et al.
(författare)
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Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors
- 1996
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Ingår i: Journal of Cardiovascular Pharmacology. - 1533-4023. ; 28:6, s. 764-768
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study was to determine the neuropeptide Y (NPY) receptor subtype responsible for the NPY-induced contraction of human subcutaneous (s.c.) resistance arteries. To elucidate this, we used (a) in vitro studies of NPY agonists: NPY, peptide YY (PYY), and Pro34NPY induced equally strong and equipotent concentration-dependent contractions of human s.c. resistance arteries, whereas NPY13-36 and NPY18-36 had no contractile effects; (b) in vitro studies using the NPY Y1-receptor antagonist, BIBP3226, which in nanomolar concentrations inhibited the contractile effect of NPY, causing a rightward shift of the concentration-response curve. pEC50 for NPY alone, 8.41 +/- 0.21; NPY + BIBP3226, 10 nM, 7.79 +/- 0.21; NPY + BIBP3226, 100 nM, 7.18 +/- 0.18; NPY + BIBP3226, 1 microM, 6.32 +/- 0.05 (n = 5-8). Schild-plot analysis indicated competitive antagonism: pA2 = 8.53 +/- 0.22 and slope = 0.99 +/- 0.14; (c) with reverse transcriptase-polymerase chain reaction (RT-PCR), we detected messenger RNA (mRNA) encoding the human NPY Y1 receptor and a splice variant of the receptor in human s.c. resistance arteries. On the basis of the agonists' potency order, the antagonistic effect of BIBP3226 on the NPY-induced contraction, and the presence of mRNA encoding the NPY Y1 receptor, we conclude that the NPY-induced contraction of human s.c. resistance arteries is mediated by NPY Y1 receptors.
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| 6. |
- Nilsson, Torun, et al.
(författare)
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Forearm blood flow responses to neuropeptide Y, noradrenaline and adenosine 5'-triphosphate in hypertensive and normotensive subjects
- 2000
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 9, s. 126-131
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY), noradrenaline (NA) and adenosine 5'-triphosphate (ATP) are important co-transmitters in the sympathetic nervous system, which has a central role in cardiovascular control. In order to evaluate if hypertension is associated with alterations in vascular responses to sympathetic co-transmitters we studied the effects of intra-arterial infusion of NPY, NA and ATP on forearm blood flow. Blood flow was measured by venous occlusion plethysmography in six hypertensive (mean arterial blood pressure (MAP) 113 +/- 4 mmHg) and six matched normotensive subjects (MAP 97 +/- 3 mmHg). NPY and NA significantly reduced forearm blood flow, while a powerful increase was seen with ATP. Forearm vascular resistance, calculated as MAP divided by forearm blood flow, was significantly increased by NPY and NA and strongly reduced by ATP. There was no difference between hypertensive and normotensive subjects in response to either transmitter. In conclusion, vascular reactivity to intra-arterial administration of NPY, NA and ATP seems to be intact in hypertensive patients without metabolic aberrations.
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| 7. |
- Porsö, Charlotta, et al.
(författare)
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Time-Dependent Climate Impact and Energy Efficiency of Internationally Traded Non-torrefied and Torrefied Wood Pellets from Logging Residues
- 2018
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Ingår i: BioEnergy Research. - : Springer Science and Business Media LLC. - 1939-1234 .- 1939-1242. ; 11, s. 139-151
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Tidskriftsartikel (refereegranskat)abstract
- Demand for wood pellets as a renewable alternative to fossil fuels has increased in the past decade. However, production and use of wood pellets involves several operations (biomass extraction, chipping, transport, drying, milling, pelleting, combustion) with negative impacts on e.g. the climate. In this study, the energy efficiency and climate impact of production and use of non-torrefied and torrefied wood pellets were analysed and compared. The wood pellets, produced from logging residues extracted from a boreal coniferous forest stand (Norway spruce (Picea abies (L.) H. Karst)) in northern Sweden, were assumed to be exported and finally used in a power plant. Time-dependent life cycle assessment, expressing the climate impact as global temperature change over time, was used to include annual greenhouse gas fluxes of both fossil and biogenic origin. The results showed that carbon stock changes due to extraction of logging residues contributed most of the warming effect on global temperature. Due to greater demand for raw material, a higher warming impact per gigajoule fuel was obtained for torrefied wood pellets than for non-torrefied wood pellets. However, torrefied wood pellets demonstrated a lower climate impact (per GJ electricity) when advantages such as higher electrical energy efficiency and higher co-firing rate were included. A general conclusion from this study is that replacing coal with non-torrefied or torrefied wood pellets made from logging residues can mitigate climate change. The energy output of these systems was about sevenfold the primary energy input.
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| 8. |
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