Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 321, Issue 4, pp 239–246 | Cite as

Energy-dependent extrusion of cyclic 3′,5′-adenosine-monophosphate

A drug-sensitive regulatory mechanism for the intracellular nucleotide concentration in rat erythrocytes
  • G. Wiemer
  • U. Hellwich
  • A. Wellstein
  • J. Dietz
  • M. Hellwich
  • D. Palm
Article

Summary

In reticulocyte-rich suspensions of red blood cells from rats extrusion of cAMP as a regulatory mechanism of intracellular cAMP was investigated.

In response to isoprenaline and/or the phosphodiesterase inhibitors Ro 20-1724 and rolipram extrusion of cAMP increases dependent on the concentration of the drugs and time of exposure. However, these drugs exert their effects on the extrusion of cAMP only indirectly, i.e. via increased intracellular levels of cAMP, since the respective EC50-values of the drugs for intracellular accumulation and extrusion of cAMP are identical (isoprenaline: ∼50 nM; rolipram: ∼1 μM; Ro 20-1724: 15 μM).

The dependence of the rate of extrusion on intracellular levels of cAMP is characterized by a typical concentration-effect relationship from which a maximal capacity of cAMP extrusion of 3–6 nmol/10 min/109 cells and a half maximal effective intracellular cAMP concentration of 40–50 nmol/109 cells can be derived. This relationship has been inferred from either kinetic or steady-state approaches. At rapidly changing intracellular levels of cAMP an apparent time lag of extracellular cAMP accumulation is obligatorily conditioned by this relationship. Vasodilating drugs which lower the ATP content of the cells as well as the uncoupler of oxidative phosphorylation, FCCP, inhibit the extrusive process (papaverine > FCCP > dipyridamole > dilazep ≫ hexobendine ≥ carbocromene) leading to a 3–5-fold increase of the intrato extracellular concentration gradient of cAMP.

It is concluded that extrusion of cAMP is a saturable and energy-dependent process which regulates the intracellular cAMP concentration independent of the activities of adenylate cyclase and phosphodiesterase.

Key words

cAMP transport Rat reticulocyte ATP Vasodilators 

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • G. Wiemer
    • 1
  • U. Hellwich
    • 1
  • A. Wellstein
    • 1
  • J. Dietz
    • 1
  • M. Hellwich
    • 1
  • D. Palm
    • 1
  1. 1.Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Geothe-UniversitätFrankfurt/MainFederal Republic of Germany

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