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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 340, Issue 6, pp 689–695 | Cite as

Effects of adenosine analogues on contractile response and CAMP content in guinea-pig isolated ventricular myocytes

  • Joachim Neumann
  • Wilhelm Schmitz
  • Hasso Scholz
  • Birgitt Stein
Article

Summary

In the present study the effects of adenosine analogues were investigated on cAMP content and contractile response in guinea-pig ventricular myocytes. The adenosine analogues (−)-N6-phenylisopropyladenosine (R-PIA), 5′-N-ethylcarboxamideadenosine (NECA) and (+)-N6-phenyl-isopropyladenosine (S-PIA) in the presence of 0.01 μmol/l isoprenaline reduced contractile response concentration-dependently. R-PIA and NECA were about equipotent (IC25: 0.01 μmol/l and 0.039 μmol/l respectively), while S-PIA was less potent (IC25: 0.6 μmol/l). Isoprenaline stimulated cAMP content was reduced by R-PIA (IC25: 0.004 μmol/l) and with lower potency by S-PIA (IC25: 0.15 μmol/l) but the extent of reduction of cAMP by R-PIA and S-PIA (to 55% and 64% respectively) was less than the reduction of contractile response (to 26% and 55% respectively). This suggests that the effects of R- and S-PIA on contractile response are only in part due to a reduction in cAMP content. In addition, NECA did not decrease cAMP content but decreased contractile response to the same extent as R-PIA. Similar results were obtained in the presence of the phosphodiesterase inhibitor Ro 20-1724. Time course studies revealed that the effects of R-PIA (1 μmol/l) on cAMP content and contractile response coincided reaching steady state after 5 min and remained stable thereafter. The effects of NECA (1 µmol/l) on contractility also reached steady state within 5 min, whereas it did not change cAMP content. It is concluded that the reduction of contractility by adenosine analogues in the presence of isoprenaline can only in part be explained by a reduction of cAMP content. It is suggested that a cAMP-independent effect, possibly an activation of phosphatases, might be involved additionally.

Key words

Adenosine analogues cAMP Isolated ventricular myocytes Contractile response Guinea-pig hearts Isoprenaline Phosphodiesterase inhibitor 

Abbreviations

R-PIA

(−)-N6-phenylisopropyladenosine

NECA

5′-N-ethylcarboxamideadenosine

S-PIA

(+)-N6-phenylisopropyl-adenosine

Ro 20-1724

4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Joachim Neumann
    • 1
  • Wilhelm Schmitz
    • 1
  • Hasso Scholz
    • 1
  • Birgitt Stein
    • 1
  1. 1.Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus EppendorfUniversität HamburgHamburg 20Germany

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