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. 1994 Apr;14(2):105–118. doi: 10.1007/BF02090779

A selective endothelin ETA antagonist, BQ-123, inhibits125I-endothelin-1 (125I-ET-1) binding to human meningiomas and antagonizes ET-1-induced proliferation of meningioma cells

Naoki Kitagawa 1,✉, Keisuke Tsutsumi 1, Masami Niwa 2, Sei-ichi Yamaga 1, Takeo Anda 1, Humayun Khalid 1, Akihiko Himeno 1, Kohtaro Taniyama 2, Shobu Shibata 1
PMCID: PMC11566749  PMID: 7842471

Abstract

1. We studied the effects of BQ-123, a selective ETA receptor antagonist, on125I-endothelin-1 (125I-ET-1) binding to cell surface receptors in surgically excised human meningiomas and on ET-1-induced DNA synthesis in cultured human meningioma cellsin vitro, using a quantitative receptor autoradiographic technique with radioluminography and3H-thymidine incorporation, respectively.

2. All of the human meningiomas expressed high-affinity binding sites for125I-ET-1, regardless of differences in histological subtypes (K d=2.6±0.2 nM,B max=374±93 fmol/mg; mean ± SE;n=9).

3. BQ-123 competed for125I-ET-1 binding to sections of meningiomas with IC50s of 3.2±0.9×10−7 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.

6. Our data suggest that (a) human meningioma cells express a large number of ETA endothelin receptors, with a small proportion of non-ETA receptors linked to proliferation of the cells, and (b) ET receptor antagonists, including BQ-123, might prove to be effective treatment for patients with meningioma.

Key words: endothelin, ETA receptor, BQ-123, meningioma, quantitative receptor autoradiography, radioluminography

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