Pharmacological Modulation of Bradykinin Receptors

Anastrozole and letrozole were purchased from Tocris Bioscience (Bristol, UK) and were diluted in 0.5% carboxymethylcellulose and 99.5% of NaCl (0.9%). Paclitaxel (6 mg/mL of Paclitaxel in Cremophor EL and dehydrated ethanol) was purchased from Glenmark (Buenos Aires, ARG) and was dissolved in NaCl (0.9%). Icatibant (kinin B₂ receptor peptide antagonist), des-Arg⁹-[Leu⁸]-bradykinin (DALBk; kinin B₁ receptor peptide antagonist) were purchased from Sigma-Aldrich Chemical Company (St. Louis MO, USA) and were also prepared in NaCl (0.9%). The enzyme immunoassay kit for bradykinin was obtained from Phoenix Pharmaceuticals, Inc. (California, USA). Specific anti-B₁ (bs-8675R–lot 9C20V14) or anti-B₂ (bs-2422R–lot AG08307921) antibodies were acquired from Bioss Antibodies (Massachusetts, USA) and secondary antibody (sc-2357–lot L1218) was obtained from Santa Cruz Biotechnology (California, USA). Paclitaxel from semisynthetic ≥ 97% (in vitro assays) was acquired from Sigma-Aldrich Chemical Company (St. Louis MO, USA). Annexin-V and 3- (4, 5-dimethyl-2-thiazolyl) -2, 5-diphenyl-2H-tetrazolium bromide] salt (MTT; 5 mg/mL solution) were obtained from Life Technologies (São Paulo, BR). The 7-Amino-Actinomycin D (7AAD) was acquired from BD Biosciences (California, USA). The doses of the drugs used in this study were based on previous studies^{13 (link),15 (link),23 (link),40 (link),72 (link)}.