Decreased digitalis receptor activity in acute rejecting canine transplanted heart
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In the course of acute rejection, myocardial tissue undergoes massive transformation and we hypothetized that for digitalis-like substances, receptor binding characteristics might be altered. Ten canine heterotopic cardiac allografts were carried out and were harvested once rejection had developed (8–10 days post-transplant). Microsomial membrane fractions of those grafts and of native hearts were isolated. Radioligand binding studies were carried out in a medium containing 5mM tris PO4, 50 mM Tris HCl, 5 mM MgCl2, pH 7.4 at 37°C, using3H-ouabain as the ligand. Saturation experiments (n=10) indicate the presence of one homogeneous population of high affinity binding sites with an affinity constant (Kd) of 8–13 nM and a maximum binding capacity (Bmax) of 47±3.5 pmol/mg protein. Both saturation and competition binding studies illustrate the fact that acute rejection resulted in a significant decrease in Bmax (43%) without significant alteration in Kd value. These studies indicate that digitalis-like substances might not exert significant inotropic activity during rejection, but this hypothesis must be confirmed by in vivo haemodynamic experiments.
Key wordshearttransplantation rejection ouabain binding sites
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