Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model.
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.
Cardoso
Ronie Cleverson
RC
Departamento de Fisiologia, Universidade Federal de Santa Catarina, Brazil. roniecardoso@hotmail.com <roniecardoso@hotmail.com>
Lobão-Soares
Bruno
B
Bianchin
Marino Muxfeldt
MM
Carlotti
Carlos Gilberto
CG
Walz
Roger
R
Alvarez-Silva
Márcio
M
Trentin
Andréa Gonçalves
AG
Nicolau
Mauro
M
D000818:Animals; D001798:Blood Proteins / Q000032:analysis*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000097:blood*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D005910:Glioma / Q000097:blood*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000819:agonists*
D001798:Blood Proteins; D043783:Receptor, Bradykinin B1; C072121:bradykinin, Sar-(D-Phe(8))des-Arg(9); D001920:Bradykinin