Der Einflu� von Reserpin auf die Wirkung der ?Neuro-Sympathomimetica?

Kuschinsky, G.; Lindmar, R.; Luellmann, H; Muscholl, E.

doi:10.1007/bf00244842

Cited by 18 publications

(4 citation statements)

References 9 publications

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“…In full agreement with various reports based on experiments with intact animals or isolated organs (Bum & Rand, 1958, 1960Kuschinsky, Lindmar, Lullmann & Muscholl, 1960;Gillespie & Mackenna, 1961), exposure to noradrenaline of isolated atria of reserpine-pretreated guinea-pigs was found to restore their response to tyramine. If this restoration of the response to tyramine were due to a simple refilling of the noradrenaline stores, then, according to Fig.…”

Section: Discussionsupporting

confidence: 91%

“…If the noradrenaline stores comprised only one compartment, this discrepancy between the expected and the observed noradrenaline content would render untenable the concept of an indirect action of tyramine. Kuschinsky et al (1960) and Muscholl (1960) found no uptake of noradrenaline into the heart of rats pretreated with reserpine; they therefore postulated that tyramine has a direct effect on cardiac tissue and that this direct action is dependent on the presence at the receptors of very small concentrations of noradrenaline.…”

Section: Discussionmentioning

confidence: 97%

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Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

Crout

Muskus

Trendelenburg

et al. 1962

British Journal of Pharmacology and Chemotherapy

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The relation between the noradrenaline content of isolated guinea-pig atria and the rate-increasing action of tyramine was studied by the use of pretreatment with reserpine as a pharmacological tool for graded depletion of the noradrenaline stores. Reserpine was more potent in depleting the stores than in reducing the biological response to tyramine; 50% depletion had little effect on the response to tyramine; 50% reduction of the response to tyramine occurred when the noradrenaline content fell to about 10% of normal. Depletion of the store's of guinea-pig atria did not result in supersensitivity to noradrenaline. Exposure of heavily pretreated atria to 3 x 106 noradrenaline for 10 min (followed by repeated washing for 45 min) restored the response to tyramine to 70% of normal; it failed, however, to restore the noradrenaline content to the level expected from the experiments with reserpine alone. Restoration of the response to tyramine was accompanied by a small but significant increase in the noradrenaline content of the atria; a change in sensitivity to added noradrenaline did not occur. The results are consistent with the view that (a) the noradrenaline stores consist of two compartments the smaller of which is important for the action of tyramine, that (b) this smaller compartment can be at least partially refilled by exposure of the atria to noradrenaline, and that (c) there is no direct relationship between the noradrenaline content and the-sensitivity to noradrenaline in guinea-pig atria.It is well known that reserpine depletes the noradrenaline stores of peripheral organs (Carlsson, Rosengren, Bertler & Nilsson, 1957;Paasonen & Krayer, 1958;Burn & Rand, 1959) and abolishes the response of such tissues to tyramine and to stimulation of adrenergic nerves (Carlsson et al., 1957;Burn & Rand, 1958;Trendelenburg & Gravenstein, 1958). Tyramine is therefore generally assumed to exert its sympathomimetic effects through the liberation of noradrenaline from peripheral noradrenaline stores. Although various studies deal with the effects of pretreatment with graded doses of reserpine, they have been restricted either to the observation of -biological responses believed to be mediated through the liberation of noradrenaline (Fleming & Trendelenburg, 1961 ;Trendelenburg, 1961;Liebman, 1961;Waud, 1961 ;Liebman, Muskus & Waud, 1962) or to the determination of catechol amine content (Carlsson et al., 1957). Since no attempt has yet been made to correlate these two phenomena quantitatively, it is not known how TYRAMINE AND NORADRENALINE STORES much the noradrenaline stores must be depleted to reduce the sympathomimetic action of tyramine.Although it is well established that noradrenaline restores the response of reserpine-pretreated preparations to tyramine (Burn & Rand, 1958, 1960 and to nerve stimulation (Burn & Rand, 1958;Gillespie & Mackenna, 1961), restoration of the noradrenaline stores has been observed by some authors (Pennefather & Rand, 1960) but not by others (Muscholl, 1960).It was thus of interest to study ...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

Crout

Muskus

Trendelenburg

et al. 1962

British Journal of Pharmacology and Chemotherapy

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“…Similarly, Leusen & Verbeke (1960) found that the sensitivity of the papillary muscle of the cat heart to the inotropic action of noradrenaline was regularly increased after reserpine pretreatment. On the other hand, Kuschinsky et al (1960) failed to observe any increase in sensitivity to noradrenaline of the atria of the rat heart after reserpine pretreatment, no matter whether rate or force of contraction were observed. This failure may be explained by the persistence of the reserpine attachment to the receptors of the rat heart.…”

Section: Discussionmentioning

confidence: 70%

“…In spite of this evidence, Kuschinsky, Lindmar, Lullmann & Muscholl (1960) consider that tyramine does not act by liberating noradrenaline, but that, in order that tyramine may act, a certain quantity of noradrenaline must be present. Their evidence is based first on the finding of Muscholl (1960) that the heart of a rat treated with reserpine does not take up noradrenaline from the blood, and, second, on the ability of very low concentrations of noradrenaline to restore the action of tyramine on the isolated atria of a reserpine-treated rat.…”

Section: Discussionmentioning

confidence: 98%

Effect of Noradrenaline on the Action of Nicotine and Tyramine on Isolated Atria

Azarnoff

Burn

1961

British Journal of Pharmacology and Chemotherapy

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Both nicotine (in the presence of atropine) and tyramine cause a rise in the rate of isolated rabbit atria. When noradrenaline is allowed to act on the atria for 20 to 30 min and then removed from the bath by repeated changes of the bath fluid, the action of nicotine and of tyramine is greatly increased. The first addition of noradrenaline to the bath often has a much smaller effect on the response to nicotine or to tyramine than have later additions. Sometimes the greater effect after the addition of nicotine persists for 2 or 3 hr. When reserpine is added to the bath and left in contact with the atria for 1 to 2 hr, and is then removed from the bath, the effect of noradrenaline on the atrial rate is much reduced in size and duration. Bretylium abolishes the action of nicotine but increases the action of tyramine.

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Noradrenalin- und Adrenalinkreis (Dopamin)

Fischer¹

1971

Vergleichende Pharmakologie Von Überträgersubstanzen in Tiersystematischer Darstellung

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Der Einflu� von Reserpin auf die Wirkung der ?Neuro-Sympathomimetica?

Cited by 18 publications

References 9 publications

Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

Effect of Tyramine on Isolated Guinea‐pig Atria in Relation to Their Noradrenaline Stores

Effect of Noradrenaline on the Action of Nicotine and Tyramine on Isolated Atria

Noradrenalin- und Adrenalinkreis (Dopamin)

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