Blockade of the inotropic effect of Bay K 8644 by cytochalasin‐B and phloretin

The positive inotropic effect in rabbit atria and papillary muscles of Bay K 8644 is blocked by cytochalasin‐B (Cyto‐B) and phloretin, two compounds known to block the facilitated diffusion of glucose. These compounds do not change the concentration‐response curve of calcium. Cyto‐B is more potent in atria than in papillary muscles, 10⁻⁷ m having a maximal effect in atria whereas 2 × 10⁻⁵m was required for a maximal effect in papillary muscles. Phloretin was fully effective at 10⁻⁴m, the only concentration tested. The inotropic effect of Bay K 8644 was virtually abolished in atria bathed in a glucose‐free medium or one containing 5 mM pyruvate. The contractile response to Bay K 8644 of papillary muscles was not changed significantly in glucose‐free or in pyruvate‐containing medium. Cyto‐B (2 × 10⁻⁵ m) caused a slight but significant increase in the K_D for the binding of nitrendipine to a crude sarcolemnal preparation from rabbit ventricles. The B_max was unchanged. These results may best be explained by the hypothesis that there is a metabolic requirement for the inotropic effect of Bay K 8644. 1988 British Pharmacological Society