gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Adenosine A1-receptor-mediated inhibition of myocardial norepinephrine release does not involve phospholipase C and protein kinase C but adenylyl cyclase

Adenosin A1-Rezeptoren vermitteln eine Phospholipase C und Proteinkinase C unabhängige aber Adenylylzyklase abhängige Inhibition der kardialen Noradrenalinfreisetzung

Meeting Abstract

  • F. Schütte - Univesitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • C. Burgdorf - Univesitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • G. Richardt - Univesitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • H. Schunkert - Univesitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)
  • T. Kurz - Univesitätsklinikum Schleswig-Holstein, Campus Lübeck (Lübeck, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP171

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Schütte et al.
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Stimulation of adenosine A1-receptors in the heart exerts cardioprotective effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings. The intraneuronal signal transduction triggered by presynaptic adenosine A1-receptors is still not completely understood. Using a pharmacological approach, we assessed the role of phospholipase C (PLC), protein kinase C (PKC), and adenylyl cyclase (AC) on adenosine A1-receptor-mediated inhibition of cardiac NE release in isolated Langendorff-perfused rat hearts. Exocytotic NE release was induced by two consecutive electrical field stimulations (5 V, 6 Hz, 1 min) and was determined in the coronary venous effluent by high-performance liquid chromatography (n = 8 each subgroup). Activation of adenosine A1-receptors with 2-chloro-N6-cyclopentyladenosine (CCPA, 0.1 µmol l-1) decreased NE release by ~ 40 % (170 ± 18 pmol g-1 vs. 293 ± 17 pmol g-1, p < 0.01). Inhibition of PLC with U 73122 (4 µmol l-1) as well as inhibition of PKC with GF 109203X (1 µmol l-1) slightly but significantly decreased NE release (U 73122: 254 ± 16 pmol g-1 vs. 292 ± 17 pmol g-1, p < 0.05; GF 109203X: 194 ± 15 pmol g-1 vs. 247 ± 15 pmol g-1, p < 0.01), however, the suppressive effect of CCPA on NE release was not modulated by U 73122 or GF 109203X. Direct activation of PKC with PMA increased NE release by ~ 30 % (504 ± 36 pmol g-1 vs. 405 ± 36 pmol g-1, p < 0.01). In contrast, blockade of AC with SQ 22536 reversed the inhibitory effect of CCPA (312 ± 25 pmol l-1 vs. 389 ± 24 pmol l-1, p < 0.01) on sympathetic neurotransmitter release irrespective of whether PKC was pharmacologically activated by PMA (479 ± 38 pmol g-1 vs. 372 ± 31 pmol g-1, p < 0.01) or was not activated. These data suggest that the adenosine A1-receptor-mediated inhibition of NE release does not involve PLC or PKC but AC.