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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 358, Issue 3, pp 360–366 | Cite as

Diminution of contractile response by κ-opioid receptor agonists in isolated rat ventricular cardiomyocytes is mediated via a pertussis toxin-sensitive G protein

  • H. Wenzlaff
  • Birgitt Stein
  • Hansjörg Teschemacher
Original article

Abstract

Opioids directly decrease the contractile response of isolated ventricular cardiomyocytes to electrical stimulation. To investigate whether these effects are mediated via GTP-binding Gi/o proteins we examined the influence of pertussis toxin on the effects of the κ-opioid receptor agonist trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U-50,488) methanesulphonate and on the as yet undescribed effects of the opioid peptide dynorphin A (1–8) on contraction. In isolated, electrically driven, rat ventricular cardiomyocytes both agents concentration dependently reduced cell shortening within 15 min, decreasing the contractile response by 79±4% (n=5) and 62±2% (n=6) of control values at maximal effective concentrations of 10 µM (U-50,488) and 1 µM [dynorphin A (1–8)], respectively. Pertussis toxin pre-treatment (200 ng/ml; 4.5–5 h) completely abolished the effects of U-50,488 and dynorphin A (1–8) on the contractile response, indicating that these effects are mediated via Gi/o proteins. In addition, the non-selective opioid receptor antagonist (–)-naloxone and the κ-opioid receptor antagonist nor-binaltorphimine antagonized the effects of U-50,488 and dynorphin A (1–8) on the contractile response. Furthermore, the µ- and δ-opioid receptor agonist (D-Ala2, D-Leu5)-enkephalin (DADLE) had no effects on contraction. These results indicate that the decrease in cell shortening is due to stimulation of κ-opioid receptors. The direct effect of κ-opioid receptor agonists on the contractile response thus represents an additional mechanism for decreasing cardiac contractility, besides the M-cholinoceptor- or adenosine receptor-mediated pathway. It is conceivable that increased release of endogenous dynorphins from the heart during hypoxia may protect the heart in a similar manner to adenosine.

Key words Cardiomyocytes Opioid receptors G proteins Pertussis toxin Dynorphin U-50 488 Naloxone Nor-binaltorphimine DADLE 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • H. Wenzlaff
    • 1
  • Birgitt Stein
    • 2
  • Hansjörg Teschemacher
    • 1
  1. 1.Rudolf-Buchheim-Institut für Pharmakologie der Justus-Liebig-Universität Gießen, Frankfurter Strasse 107, D-35392 Gießen, GermanyDE
  2. 2.Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, D-20246 Hamburg, GermanyDE

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