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  • Noradrenaline Metabolites  (5)
  • Noradrenaline release  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 276 (1973), S. 71-88 
    ISSN: 1432-1912
    Keywords: Noradrenaline Metabolites ; Guinea-Pig Atria ; Nictitating Membrane ; Normetanephrine ; Metanephrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the five noradrenaline (NA) metabolites and of the O-methylated metabolite of adrenaline, metanephrine, were studied in a tissue with adrenergic beta-receptors (guinea-pig atria) and in a tissue with predominance of alpha-receptors (cat's nictitating membrane). In atria, normetanephrine and metanephrine elicited positive chronotrophic effects which were mediated through the beta-receptors. Both O-methylated metabolites had only 1/1000th of the potency of NA. In the normally innervated nictitating membrane normetanephrine and metanephrine elicited maximal responses of the same magnitude as NA. While normetanephrine had one half of the potency of NA, metanephrine was even more potent than NA. The effects of normetanephrine or metanephrine were mediated through the activation of the alpha-receptors and were not potentiated by either cocaine or denervation. Neither the deaminated nor the deaminated-O-methylated metabolites of NA had activity as agonists on alpha-or beta-receptors in concen-of up to 1×10−4M. These metabolites did not elicit alpha-or beta-receptor block in concentrations of up to 1×10−4M.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 243-259 
    ISSN: 1432-1912
    Keywords: Scorpion Toxin ; Noradrenaline ; Noradrenaline Metabolites ; Guinea-Pig Atria ; Nerve Stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of a purified fraction of the venom of the Brazilian scorpion, Tityus serrulatus, were studied in isolated guinea-pig atria previously labelled with 3H-noradrenaline. Exposure to 0.3 and 1.0 μ/ml of the scorpion toxin resulted in a long lasting positive chronotropic effect which was concentration-dependent. The increase in atrial rate coincided with an enhancement in spontaneous outflow of radioactivity. The increase in outflow of radioactive products elicited by exposure to 1.0 μg/ml of the scorpion toxin was approximately 3-fold. 3H-noradrenaline accounted for 60% of the total increase in outflow of radioactivity elicited by the scorpion toxin and the 3H-deaminated glycol (3,4-dihydroxyphenylglycol) represented the main metabolite formed, accounting for approximately 35% of the total release. 20 min after exposure to 1.0 μg/ml of the scorpion toxin the overflow of the labelled transmitter elicited by accelerans nerve stimulation (4 Hz, during 60 sec, supramaximal voltage) was increased 8-fold. This effect of the scorpion toxin appears to be unrelated to inhibition of neuronal uptake, block of α-adrenoceptors or stimulation of β-adrenoceptors. Consequently, in addition to releasing noradrenaline, the scorpion toxin enhances transmitter overflow elicited by nerve stimulation through a prejunctional effect which appears to reflect a nove mechanism of action.
    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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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 278 (1973), S. 179-194 
    ISSN: 1432-1912
    Keywords: Noradrenaline ; Noradrenaline Metabolites ; Perfused Spleen ; Nerve Stimulation ; Transmitter Overflow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic pathway of 3H-noradrenaline released spontaneously and by nerve stimulation was studied in the isolated perfused spleen of the cat. The deaminated glycol, DOPEG, (3,4 dihydroxyphenylglycol) was the main metabolite in spontaneous outflow, accounting for 62.5±1.6% of the total radioactivity (n=13). Of the total increase in radioactive products elicited by nerve stimulation at 5 Hz or 10 Hz around 30% was accounted for by the noradrenaline metabolites, particularly DOPEG and the O-methylated fraction. In the presence of 2.9×10−6 M of cocaine the total overflow of radioactivity induced by stimulation was unchanged but DOPEG formation from released noradrenaline was abolished. These findings indicate that DOPEG formation results from the recapture of the released transmitter by adrenergic nerve endings and subsequent intraneuronal deamination. The total overflow of noradrenaline was reduced by flow-stop while the metabolism of the released transmitter was increased significantly. Cocaine, 2.9×10−6 M, prevented the increase in DOPEG when stimulation was applied under flow-stop conditions. The decrease in noradrenaline overflow induced by flow-stop is partly due to the increase in the metabolism of the released transmitter.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    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.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 280 (1973), S. 315-330 
    ISSN: 1432-1912
    Keywords: Tyrosine Hydroxylase ; Noradrenaline ; Noradrenaline Metabolites ; Dopa Decarboxylase ; Guinea-pig Atria ; Noradrenaline Synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of noradrenaline, its five metabolites and metanephrine, were studied on tyrosine hydroxylase activity in guinea-pig atria. The deaminated metabolite, (±)-3,4-dihydroxyphenylglycol (DOPEG), was equipotent with (±)-noradrenaline in its inhibitory action on tyrosine hydroxylase activity in the homogenates of guinea-pig atria. The inhibition by DOPEG was competitive with the cofactor, reduced pteridine. The deaminated acid, 3,4-dihydroxymandelic acid (DOMA) and the O-methylated deaminated acid, 3-methoxy, 4-hydroxymandelic acid (VMA) had 1/50th and 1/30th, respectively, the potency of noradrenaline in inhibiting tyrosine hydroxylase. The rest of the metabolites did not inhibit tyrosine hydroxylase in homogenates in concentrations up to 1.0 mM. In intact guinea-pig atria noradrenaline was considerably more potent than DOPEG in inhibiting tyrosine hydroxylase. Normetanephrine 1.4×10−4 M inhibited tyrosine hydroxylase in the intact tissue but failed to inhibited the enzyme in the homogenate even in higher concentrations. The effect of normetanephrine in the intact tissue is related to the ability of this compound to release endogenous noradrenaline. A reserpine-like agent, Ro 4-1284, did not inhibit tyrosine hydroxylase activity in the homogenate but in the intact tissue the inhibition was more than 50%. This effect of Ro 4-1284 in the intact tissue appears to be related to the releasing effects of this agent and to an increase in the axoplasmic levels of DOPEG. Since the formation of the deaminated glycol, DOPEG, represents the main metabolic pathway for the neurotransmitter in adrenergic nerve endings, the present results are compatible with the view that, in addition to the pool of extravesicular noradrenaline, the cytoplasmic concentration of DOPEG could also participate in the regulation of the activity of tyrosine hydroxylase.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1912
    Keywords: Nerve Stimulation ; Noradrenaline Metabolites ; Hydrocortisone ; Extraneuronal Uptake ; Normetanephrine ; Nictitating Membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolism of 3H-noradrenaline released by nerve stimulation in the isolated nerve-muscle preparation of the cat nictitating membrane was determined under control conditions and in the presence of hydrocortisone, 28 μM, a concentration which inhibits the high affinity extraneuronal uptake of noradrenaline in this tissue. in the controls the main fraction in the overflow elicited by stimulation at 10 Hz during 2 min was the deaminated glycol, 3H-DOPEG (3,4-dihydroxyphenylglycol), which accounted for 45.2±2.96% of the total radioactivity. Under these conditions, 3H-noradrenaline represented 30.8±1.92%, while 3H-normetanephrine accounted for 14.5±0.94% of the total overflow of radioactivity. During exposure to hydrocortisone there was a selective inhibition in 3H-normetanephrine formation from 3H-noradrenaline released by stimulation while the other fractions were not affected significantly. In contrast to these results, there were no changes in the spontaneous outflow of 3H-normetanephrine during exposure to hydrocortisone. The results obtained support the view that 3H-normetanephrine in sponteneous release originates from the activity of prejunctional catechol-O-methyltransferase. On the other hand, 3H-normetanephrine formed during transmitter release elicited by nerve stimulation is due to the activity of extraneuronal catechol-O-methyltransferase. Access of 3H-noradrenaline released by nerve stimulation to extraneuronal catechol-O-methyltransferase is mediated through the high-affinity, hydrocortisone-sensitive extraneuronal uptake mechanism.
    Type of Medium: Electronic Resource
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