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Evidence for a cell surface adenosine receptor on coronary myocytes and atrial muscle cells

Studies with an adenosine derivative of high molecular weight

Summary

We have studied the site of action of adenosine with the aid of a large molecular weight adenosine derivative which is confined to the extracellular space. A stable protein-AMP-conjugate was formed using 1-ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide to covalently couple AMP by P-N linkage to lysine residues of a carbonic anhydrase preparation. The conjugate was characterized by disc-SDS-electrophoresis and exhibited a mean molecular weight of about 30000. When infused into the coronary arteries of isolated guinea pig hearts the protein-AMP-conjugate induced vasodilation which was similar in magnitude and time course to that elicited by free AMP or adenosine. The dilatory response of the coronaries was caused by the protein-AMP-conjugate itself and not by free AMP or by adenosine liberated from the conjugate. This conclusion is based on the facts that: i) The electrophoretic mobility of the conjugate remained unchanged after its passage through the heart. ii) Addition of 5′-nucleotidase and adenosine deaminase to the protein-AMP-conjugate prior to its infusion into the coronaries did not alter the vasoactive effects. iii) Perfusion of the isolated hearts with equipotent concentrations of14C-AMP,14C-adenosine or protein-14C-AMP-conjugate resulted in a significant incorporation of radioactivity into cardiac adenine nucleotides only in the case of labeled AMP and adenosine. Besides its effects on the coronaries, the protein-AMP-conjugate also rapidly abolished the calcium-dependent action potential in the atrial muscle. Since the biological effects observed are most likely caused by the adenosine moiety of AMP our results provide evidence that AMP as well as adenosine act via a receptor site on the surface of coronary myocytes and atrial muscle cells.

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Schrader, J., Nees, S. & Gerlach, E. Evidence for a cell surface adenosine receptor on coronary myocytes and atrial muscle cells. Pflugers Arch. 369, 251–257 (1977). https://doi.org/10.1007/BF00582192

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Key words

  • Isolated heart
  • Vascular permeability
  • Myocardial blood flow
  • Adenosine
  • Adenosine receptor