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Release of noradrenaline by one pulse: Modulation of such release by alpha-adrenoceptor antagonists and uptake blockers

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Summary

  1. 1.

    The primary aim of this work was two-fold. To introduce a simpe method for studying sympathetic neurosecretion in the mammalian heart in response to nerve stimulation. The other aim was to determine whether or not presynaptic alpha-adrenoceptors and high affinity uptake mechanism of cardiac sympathetic nerves play some role in the regulation of nordrenaline release evoked by one pulse.

  2. 2.

    Nordrenaline overflow induced by a train of impulses (1 Hz for 180 s) in the isolated perfused heart of the guinea pig was enhanced in a dose-dependent manner by phentolamine or phenoxybenzamine, and the extent of enhancement was comparable.

  3. 3.

    Nordrenaline overflow was not altered upon excitation of sympathetic nerve by one pulse. Addition of phentolamine, phenoxybenzamine, yohimbine or uptake blockers (cocaine, desipramine and corticosterone) to the perfusion medium did not modify the overflow.

  4. 4.

    Nordrenaline overflow induced by one pulse was enhanced by K-channel blockers (4-aminopyridine or tetraethylammonium, TEA).

  5. 5.

    3H-nordrenaline overflow induced by one shock in the presence of TEA was further enhanced almost two-fold by alpha-adrenoceptor antagonists. At 1 Hz, these agents enhanced the overflow also two-fold.

  6. 6.

    The overflow of 3H-noradrenaline induced by one shock or 1 Hz (in the presence of TEA) was enhanced over two-fold by desipramine.

  7. 7.

    Our conclusion is that the release of sympathetic tranmitter upon one shock is under the control of presynaptic alpha-adrenergic receptors. Accordingly, noradrenaline released in the very early part of the exocytosis could interfere with the remaining part of the same release process by modulating the availability of calcium. The present findings also show that the neuronal uptake process plays an important role in removing noradrenaline released even after one pulse.

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Author notes

  1. Arun R. Wakade & Taruna D. Wakade

    Present address: Department of Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, 11203, Brooklyn, NY, USA

Authors and Affiliations

  1. Abteilung Neurochemie, Max-Planck-Institut für Psychiatrie, D-8033, Martinsried bei München, Germany

    Arun R. Wakade & Taruna D. Wakade

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  1. Arun R. Wakade
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  2. Taruna D. Wakade
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This material is based upon work supported in part by the National Science Foundation Grant BNS 79-23019 and in part by the National Institutes of Health Grant HL-18601

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Wakade, A.R., Wakade, T.D. Release of noradrenaline by one pulse: Modulation of such release by alpha-adrenoceptor antagonists and uptake blockers. Naunyn-Schmiedeberg's Arch. Pharmacol. 317, 302–309 (1981). https://doi.org/10.1007/BF00501310

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  • DOI: https://doi.org/10.1007/BF00501310

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