On the Specificity of Binding of Prostaglandins to Coronary Arteries — Correlation to the Biological Response

  • U. Fricke
  • K. Schrör

Abstract

The relationship of prostaglandin (PGE1, PGE2) binding and biological response was studied on isolated bovine coronary arteries. Tension development of helically cut strips was measured isometrically (preload: 2 gms) in modified Tyrode solution (37°C, pH 7.4). The binding (tissue/medium ratio) was determined simultaneously in strips of the same vessels using 3H-PGE1, 3H-PGE2. Binding at conditions without biological response was estimated in Tris-buffer (50 mM, pH 7.4). The binding and biological activity of 14C-linoleic acid (LA) was studied in the same manner. Cumulative application of PGE2 (0.2 – 177 μM) was followed by a concentration-dependent increase in both tension development (max = 0.79 ± 0.13 g, ED-50 = 6 μM. n=7) and binding (max = 0.94 ± 0.07, n=6). Pretreatment with indomethacin (3 μM) did not alter biological response or binding (n=4). With PGE1 (0.04 – 177 μM) there was a small relaxation followed by a final contraction. Strips, previously contracted by PGE2 (20 μM) responded only with relaxation (max = 0.46 ± 0.06 g, ED-50 = 4 μM, n=7). This was parallelled by an increase in binding (max = 1.45 ± 0.06, n=6), which was significantly higher than in nonpretreated strips (max = 1.15 ± 0.03, n=6). Binding of PGE1 and PGE2 in Tris-buffer gave similar curves shifted, however, to lower values (0.80 ± 0.05, n=6, 0.97 ± 0.07, n=6). With LA (0.2 – 221 μM) there was neither biological response nor difference in binding between Tris and Tyrode solutions (max = 13.31 ± 0.98, n=6; max = 13.34 α 1.02, n=6). Plotting the biological response in dependence on the tissue binding resulted in a linear correlation over a wide concentration range (0.4–40 μM) for both prostaglandins. This investigation of binding close to physiological situations provides evidence for prostaglandin binding sites mediating their coronary vasomotory response. (Supported by the Deutsche Forschungsgemeinschaft: Schr 194/2)

Keywords

Fluori Adenosine Prostaglandin Sine Indomethacin 

Copyright information

© Springer-Verlag Berlin Heidelberg 1978

Authors and Affiliations

  • U. Fricke
    • 1
  • K. Schrör
    • 1
  1. 1.Pharmakologisches InstitutUniversität zu KölnKöln 41Germany

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