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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 320 (1982), S. 26-33 
    ISSN: 1432-1912
    Keywords: Convulsions ; Noradrenaline release ; Cerebral cortex ; Brain stem ; MOPEG levels ; Quaking mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Quaking mouse is a genetically determined model of convulsive disorders. We investigated the modulation of noradrenergic neurotransmission through α2-adrenoceptors in the occipital cortex and the brain stem of this mutant. The endogenous levels of noradrenaline were similar in the cerebral cortex of the Quaking mice and their corresponding controls, while a significant increase of endogenous noradrenaline was found in the brain stem of the mutants. The rate of disappearance of noradrenaline in the cerebral cortex and the brain stem after injection of FLA 63 was identical in control and Quaking mice. The calciumdependent electrically evoked overflow of 3H-noradrenaline from slices of occipital cortex was inhibited by clonidine and enhanced by yohimbine in Quaking as well as in normal mice. The negative feed-back mechanism mediated by presynaptic α2-adrenoceptors operates to a similar extent in both strains of mice. In contrast to the occipital cortex, in the brain stem, the amount of neurotransmitter released by electrical stimulation was significantly increased in Quaking mice when compared with the controls. However, in the brain stem, the negative feed-back regulation of noradrenaline release operates to a similar extent in both strains of mice. When the endogenous levels of MOPEG were determined in the brain stem, they were found to be significantly higher in the Quaking mice when compared to the controls. The results suggest that an increase in noradrenergic neurotransmission in the brain stem, rather than in the cerebral cortex, could contribute to the behavioural abnormalities exhibited by the Quaking mice.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Noradrenaline release ; Tityustoxin ; Nictitating membrane ; Hypothalamus ; Cerebral cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated nerve-muscle preparation of the cat nictitating membrane exposure to 0.04 μM of the scorpion venom tityustoxin (TsTX) increased significantly the overflow of 3H-noradrenaline and the responses elicited by postganglionic nerve stimulation (1200 pulses, 0.5 ms duration, supramaximal voltage). Concentration effect curves to exogenous (-)-noradrenaline were not affected in the presence of this concentration of TsTX. The enhanced release of 3H-noradrenaline obtained during nerve stimulation as well as the increase of the postsynaptic responses observed during exposure to TsTX were more pronounced at 4 Hz than at 20 Hz. The increase in the overflow of noradrenaline observed with the toxin was selective for nerve stimulation since the release evoked by tyramine was not affected by TsTX. TsTX did not increase further the enhancement of 3H-noradrenaline release obtained in the presence of 18 mM tetraethylammonium (TEA). On the other hand, both TsTX and TEA were able to increase further the overflow of 3H-noradrenaline after block of the presynaptic alpha-adrenoceptors with phenoxybenzamine 0.29 or 2.9 μM. In slices of rat cerebral cortex, TsTX 0.04 μM increased 3H-noradrenaline release induced by 10 mM and by 20 mM KCl. The increased release evoked by the toxin was more pronounced for the lower concentration of K+. An increased release of 3H-noradrenaline in the presence of the toxin was also observed in rat hypothalamic slices stimulated with 20 mM K+. The K+ stimulated induced release of 3H-noradrenaline was also increased by 1.8 mM TEA. As shown for the peripheral nervous, system the simultaneous addition of TEA and TsTX did not result in additive effects when compared with the effects of the two agents added separately. Tityustoxin did not modify the metabolic pattern of the neurotransmitter released by K+ from rat hypothalamic slices. It is concluded that TsTX increases the stimulation-induced release of 3H-noradrenaline from both peripheral and central noradrenergic nerve terminals. Tityustoxin appears to act on the nerve terminal by a mechanism similar to that of TEA, an agent known to enhance the amount of noradrenaline released by nerve stimulation by increasing the duration of the action potentials.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 332 (1986), S. 384-390 
    ISSN: 1432-1912
    Keywords: α,β-Methylene ATP ; SHR ; WKY-tail arteries ; Periarterial field stimulation ; Noradrenaline release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of α,β-methylene-adenosine triphosphate, (α,β-methylene ATP, a P2-receptor desensitising agent) have been evaluated on vasoconstrictor responses elicited by exogenous agonists or electrical field stimulation in isolated perfused SHR or WKY tail arteries and on tritium release elicited by electrical field stimulation in SHR-tail arteries pre-labeled with 3H-noradrenaline. Exposure to α,β-methylene ATP (0.1 μmol/l) significantly inhibited vasoconstrictor responses to electrical field stimulation in SHR tail arteries. These inhibitory effects were not further increased at a higher concentration of α,β-methylene ATP (1 μmol/l). In WKY tail arteries, α,β-methylene ATP (1 μmol/l) failed to significantly inhibit vasoconstrictor responses to electrical stimulation. In SHR tail arteries prelabelled with 3H-noradrenaline, α,β-methyleneATP (1 μmol/l) did not inhibit the stimulation evoked release of tritium. However, at this concentration, α,β-methylene ATP significantly antagonized the vasoconstrictor responses of SHR tail arteries induced by exogenous ATP (1 μmol/l), β,γ-methylene ATP (30 μmol/l), a stable agonist at P2-receptors, or 60 mmol/l KCl. These effects of α,β-methylene ATP on contractile responses to KCl were not observed in WKY-tail arteries. In tail arteries obtained from reserpine pretreated SHR, despite a 85–95% decrease in endogenous noradrenaline tissue content, the vasoconstrictor responses induced by periarterial field stimulation were greatly diminished, but not abolished. These residual responses to periarterial field stimulation were not antagonized by prazosin (0.1 μmol/l), but were practically abolished by the addition of α,β-methylene ATP (1 μmol/l). In tail arteries from WKY rats pretreated with reserpine, exposure to prazosin (0.1 μmol/l) further reduced the residual responses elicited by electrical field stimulation. In these WKY-tail arteries, addition of α,β-methylene ATP (1 μmol/l) did not further inhibit the remaining vasoconstrictor response obtained in the presence of prazosin. While our results suggest a significantly greater cotransmitter role for ATP with noradrenaline in tail arteries of SHR compared with control normotensive WKY rats, additional effects of α,β-methylene ATP not involving P2 receptors cannot be entirely excluded.
    Type of Medium: Electronic Resource
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