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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 358, Issue 4, pp 440–444 | Cite as

Modulation of noradrenaline release from the sympathetic nerves of human right atrial appendages by presynaptic EP3- and DP-receptors

  • G. J. Molderings
  • James Likungu
  • Manfred Göthert
Original article

Abstract

Strips of human right atrial appendages were preincubated with [3H]noradrenaline and then superfused with physiological salt solution containing inhibitors of uptake1 and uptake2. Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). Prostaglandin E2 (PGE2) inhibited the electrically evoked tritium overflow; at the highest concentration investigated, tritium overflow was reduced by about 80% and the pIC50% value was 7.14. The effect of PGE2 was not affected by rauwolscine, which, by itself, increased the evoked overflow. Naproxen failed to affect the evoked tritium overflow and its inhibition by PGE2. The inhibitory effect of PGE2 on the electrically evoked tritium overflow was mimicked by prostaglandin E1, the EP1/EP3-receptor agonist sulprostone and the EP2/EP3-receptor agonist misoprostol with the rank order of potency (pEC50%): sulprostone (7.68) > misoprostol (7.10) > PGE1 (6.39). In contrast, PGF, the IP/EP1-receptor agonist iloprost and the stable thromboxane A2 analogue U46619 (9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F) did not change evoked tritium overflow. PGD2 caused facilitation. These results suggest that the sympathetic nerve fibres innervating human atrial appendages are endowed with presynaptic inhibitory EP3 and facilitatory DP-receptors. The EP3-receptors appear not to be tonically activated and do not interact with the α2-autoreceptors.

Key words Human atrial appendage EP3-receptors DP-receptors Presynaptic receptors Noradrenaline release 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. J. Molderings
    • 1
  • James Likungu
    • 2
  • Manfred Göthert
    • 1
  1. 1.Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstrasse 2b, D-53113 Bonn, Germany e-mail: molderings@ibm.rhrz.uni-bonn.de, Fax: +49-228-735404DE
  2. 2.Klinik für Herz-und Gefäßchirurgie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, GermanyDE

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