Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model

Abstract Background While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model. Results SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area. Conclusions Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

We would like to thank Dr. Vivaldo Moura Neto, Departamento de Anatomia e Histologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil,, for kindly providing C6 cells from his personal cell bank, and Dr. Domenico Regoli, Université de Sherbrooke, Sherbrooke, Québec, Canada, for providing SardesArg9. This work was funded by Capes, CNPq and FunpesquisaUFSC. Dr Bianchin was supported by FAPESP (02/037430). The authors are indebted to Elettra Greene for revising the English text.

We would like to thank Dr. Vivaldo Moura Neto, Departamento de Anatomia e Histologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil,, for kindly providing C6 cells from his personal cell bank, and Dr. Domenico Regoli, Université de Sherbrooke, Sherbrooke, Québec, Canada, for providing Sar-[D-Phe8]des-Arg9. This work was funded by Capes, CNPq and Funpesquisa-UFSC. Dr Bianchin was supported by FAPESP (02/03743-0). The authors are indebted to Elettra Greene for revising the English text.