Summary: Endothelin-1 (ET-1) has been shown to cooper??e with other growth factors to enhance mitogenesis of ??roblasts and vascular smooth-muscle cells (SMCs) in ??ro. One possible mechanism underlying such enhance??nt is the comodulation of receptor density/affinity for ??e factor by the other. In previous work, we showed that ??etreatment of Swiss 3T3 fibroblasts with such growth ??tors as epidermal growth factor (EGF), platelet-de-??ed growth factor (PDGF), or basic fibroblast growth ??ctor (bFGF) resulted in increased binding of 1251-ET-1 ??these cells by two-, four-, and fivefold, respectively. ??o determine whether similar effects occur in human ??lls, 125I-ET-1 binding to early-passage human aortic ??MCs was examined in untreated cells and in cells pre??eated for 16 h with 1.0 nM of EGF, PDGF, or bFGF. In untreated cells, Scatchard analysis confirmed 26,500 ± 2,000 (n = 4) binding sites with an apparent Kd of 105 ± 53 pM. Pretreatment with EGF increased the number of binding sites to 36,500 ± 4,950 (n = 3) with no significant change in Kd (128 ± 38 pM). Similarly, pretreatment with 1.0 nM bFGF also increased the number of 125I-ET-1 binding sites to 34,000 ± 1,700 (n = 3) with no significant change in Kd (94 ± 13 pM). Unlike EGF and bFGF, pretreatment with PDGF-BB resulted in a decrease of 125I-ET-1 binding sites (14,600 ± 2,300 sites/cell; n = 3) with no significant change in Kd (95 ± 23 pM). These results extend our previous observations with murine fibroblasts and may provide an important insight into the regulation of ET activity, particularly under pathological conditions.