IDENTIFICATION AND BIOCHEMICAL-CHARACTERIZATION OF A HEART-MUSCLE CELL TRANSFORMING GROWTH-FACTOR-BETA-1 RECEPTOR

Binding of human-recombinant transforming growth factor-beta1 (TGF-beta1) to the neonatal rat heart-muscle cell (cardiomyocyte) was characterized as a potential element in the cardioprotective pharmacology of this growth factor. The cardiomyocytes were found to express a single class of specific, high-affinity TGF-beta1 binding sites. Ligand binding to these sites was rapid, saturable, selective, and reversible, characteristics of a receptor-mediated process. Scatchard and iterative non-linear least-squares regression analyses demonstrated that the cardiomyocyte TGF-beta1 receptor had a K(d) less-than-or-equal-to 40 pM, a B(max) of approximately 3.4 fmol/10(6) cells, and a density of approximately 2000 binding sites/cell. Binding was selective for TGF-beta1 as compared with other TGF-beta isoforms (i.e. TGF-beta2 and -beta3) and nonrelated cytokines (e.g. acidic fibroblast growth factor). Affinity-binding experiments to probe the molecular nature of the specific binding revealed three types of cardiomyocyte TGF-beta1 binding proteins, the most prominent of which corresponded to the high-molecular-mass proteoglycan observed in nonmuscle cell types. These data raise the possibility that the known pharmacological effects of TGF-beta1 on heart muscle may be direct actions via specific receptor-mediated events.