| 1. |
- Jolkkonen, Mikael, et al.
(författare)
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Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors
- 2001
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Ingår i: Toxicon. - 0041-0101 .- 1879-3150. ; 39:2-3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [H-3]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K-d = 5.3 mu M. The binding mechanism of MT alpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K-T = 3.8 mu M) was followed by a slow process of isomerisation of this complex (k(i) = 1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K-T = 1.4 mu M, k(i) = 8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.
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| 2. |
- Jolkkonen, Mikael, et al.
(författare)
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Thermo-chemical modelling of uranium-free nitride fuels
- 2004
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Ingår i: Journal of Nuclear Science and Technology. - : Informa UK Limited. - 0022-3131 .- 1881-1248. ; 41:4, s. 457-465
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Tidskriftsartikel (refereegranskat)abstract
- A production process for americium-bearing, uranium-free nitride fuels was modelled using the newly developed ALCHYMY thermochemical database. The results suggested that the practical difficulties with yield and purity are of a kinetic rather than a thermodynamical nature. We predict that the immediate product of the typical decarburisation step is not methane, but hydrogen cyanide. HCN may then undergo further reactions upon cooling, explaining the difficulty in observing any carbophoric molecules in the gaseous off stream. The thermal stability of nitride fuels in different environments was also estimated. We show that sintering of nitride compounds containing americium should be performed under nitrogen atmosphere in order to the avoid the excessive losses of americium reported from sintering under inert gas. Addition of nitrogen in small amounts to fuel pin filling gas also appears to significantly improve the in-pile stability of transuranium nitride fuels.
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| 3. |
- Karlsson, E., et al.
(författare)
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Snake toxins with high selectivity for subtypes of muscarinic acetylcholine receptors
- 2000
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Ingår i: Biochimie. - 0300-9084 .- 1638-6183. ; 82:9-10, s. 793-806
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Tidskriftsartikel (refereegranskat)abstract
- There are five subtypes of muscarinic acetylcholine receptors (M-1 to M-5) which control a large number of physiological processes, such as the function of heart and smooth muscles, glandular secretion, release of neurotransmitters, gene expression and cognitive functions as learning and memory. A selective ligand is very useful for studying the function of a subtype in presence of other subtypes, which is the most common situation, since a cell or an organ usually has several subtypes. There are many non-selective muscarinic ligands, but only few selective ones. Mambas, African snakes of genus Dendroaspis have toxins, muscarinic toxins, that are selective for M-1, M-2 and M-4 receptors. They consist of 63-66 amino acids and four disulfides which form four loops. They are members of a large group of snake toxins, three-finger toxins; three loops are extended like the middle fingers of a hand and the disulfides and the shortest loop are in the palm of the hand. Some of the toxins target the allosteric site which is located in a cleft of the receptor molecule close to its extracellular part. A possible explanation to the good selectivity is that the toxins bind to the allosteric site, but because of their size they probably also bind to extracellular parts of the receptors which are rather different in the various subtypes. Some other allosteric ligands also have good selectivity, the alkaloid brucine and derivatives are selective for M-1, M-3 and M-4 receptors. Muscarinic toxins have been used in several types of experiments. For instance radioactively labeled M-1 and M-4 selective toxins were used in autoradiography of hippocampus from Alzheimer patients. One significant change in the receptor content was detected in one region of the hippocampus, dentate gyrus, where M-4 receptors were reduced by 50% in patients as compared to age-matched controls. Hippocampus is essential for memory consolidation. M-4 receptors in dentate gyrus may play a role, since they decreased in Alzheimers disease which destroys the memory. Another indication of the role of M-4 receptors for memory is that injection of the M-4 selective antagonist muscarinic toxin 3 (M-4-toxin 1) into rat hippocampus produced amnesia.
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| 4. |
- Nasman, J., et al.
(författare)
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Recombinant expression of a selective blocker of M-1 muscarinic receptors
- 2000
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 271:2, s. 435-439
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Tidskriftsartikel (refereegranskat)abstract
- Mamba venoms contain peptides with high selectivity for muscarinic receptors, Due to the limited availability of the M-1 muscarinic receptor-selective MT7 or ml-toxin 1, the peptide was expressed in Sf9 cells using a synthetic cDNA and purified, The isolated peptide had over four orders of magnitude higher affinity for the M-1 compared to M-2-M-5 muscarinic receptors, The peptide strongly inhibited Ca2+ mobilisation ;through recombinant and endogenously expressed M-1 receptors, having no effect on the function of the other subtypes. The MT7 peptide provides a unique tool for identification and functional characterisation of M-1 receptors in cells and tissues,
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