Decreased digitalis receptor activity in acute rejecting canine transplanted heart.
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). Microsomal membrane fractions of those grafts and of native hearts were isolated. Radioligand binding studies were carried out in a medium containing 5 mM Tris PO4, 50 mM Tris HCl, 5 mM MgCl2, pH 7.4 at 37 degrees C, using 3H-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.
Dumont
L
L
Départment de pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Trelles
L
L
Chartrand
C
C
D000818:Animals; D001665:Binding Sites; D004071:Digitalis Glycosides / Q000378:metabolism*; D004285:Dogs; D006084:Graft Rejection; D016027:Heart Transplantation; D010042:Ouabain / Q000378:metabolism; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase
D004071:Digitalis Glycosides; D011955:Receptors, Drug; C027082:digitalis receptor; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase