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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 306, Issue 3, pp 241–248 | Cite as

Effects of papaverine and its interaction with isoprenaline and carbachol on the contractile force and cyclic nucleotide levels of the canine ventricular myocardium

  • M. Endoh
  • M. Honma
Article

Summary

In the isolated ventricular myocardium of the dog the effects of papaverine on the contractile force and on the cyclic nucleotide levels were studied. Furthermore the interaction between papaverine and the adrenergic β-or cholinergic stimulation was investigated.
  1. 1.

    Papaverine (3×10−5 M) induced a positive inotropic action and increased the cyclic AMP level in the majority of preparations. Ventricular muscles isolated from certain dogs showed only a negative inotropic response to papaverine. As a whole, a significant correlation was found between the tension developed and the cyclic AMP level after the administration of papaverine. The cyclic GMP level was not changed or decreased by papaverine.

     
  2. 2.

    The positive inotropic action of papaverine and elevation of the cyclic AMP level in response to papaverine were not inhibited by a β-adrenoceptor blocking drug, pindolol (3×10−8 M), indicating that these effects are not caused by catecholamine release.

     
  3. 3.

    In muscles, in which papaverine failed to cause the positive inotropic action, contractile as well as cyclic AMP responses to isoprenaline were significantly enhanced by papaverine.

     
  4. 4.

    Carbachol (3×10−6M) diminished the positive inotropic actions of isoprenaline and papaverine, abolished the accumulation of cyclic AMP produced by these agents, and increased significantly the cyclic GMP level. The elevation of cyclic GMP level by carbachol in the presence of papaverine was especially marked and amounted to 4-fold the corresponding control value. These results indicate that papaverine inhibits the break down of the intracellular cyclic AMP and GMP in the intact myocardial cells and may thereby interact functionally with the autonomic nervous system.

     

Key words

Papaverine Isoprenaline Carbachol Cyclic AMP Cyclic GMP Ventricular contraction 

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Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • M. Endoh
    • 1
  • M. Honma
    • 1
  1. 1.Department of PharmacologyTohoku University School of MedicineSendaiJapan

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