A selective endothelin ETA antagonist, BQ-123, inhibits 125I-endothelin-1 (125I-ET-1) binding to human meningiomas and antagonizes ET-1-induced proliferation of meningioma cells.

1. We studied the effects of BQ-123, a selective ETA receptor antagonist, on 125I-endothelin-1 (125I-ET-1) binding to cell surface receptors in surgically exercised human meningiomas and on ET-1-induced DNA synthesis in cultured human meningioma cells in vitro, using a quantitative receptor autoradiographic technique with radioluminography and 3H-thymidine incorporation, respectively. 2. All of the human meningiomas expressed high-affinity binding sites for 125I-ET-1, regardless of differences in histological subtypes (Kd = 2.6 +/- 0.2 nM, Bmax = 374 +/- 93 fmol/mg; mean +/- SE; n = 9). 3. BQ-123 competed for 125I-ET-1 binding to sections of meningiomas with IC50S of 3.2 +/- 0.9 x 10(-7) M, and 10(-4) M BQ-123 displaced 80% of the binding. 4. ET-1 significantly stimulated DNA synthesis in cultured human meningioma cells, up to 170% of the basal level in the presence of 10(-9) M ET-1. BQ-123 inhibited ET-1 (10(-9) M)-induced DNA synthesis in meningioma cells, in a dose-dependent manner, and 10(-5) M BQ-123 reduced it to 120% of the basal level. 5. The number of meningioma cells determined after 4 days in culture was dose dependently increased in the presence of ET-1 (10(-9) and 10(-7) M). The growth rate of meningioma cells, incubated with 10(-9) M ET-1, was reduced by 50% in the presence of 10(-7) M BQ-123.(ABSTRACT TRUNCATED AT 250 WORDS)