PERMEABILITY OF THE BLOOD-BRAIN-BARRIER BY THE BRADYKININ AGONIST, RMP-7 - EVIDENCE FOR A SENSITIVE, AUTO-REGULATED, RECEPTOR-MEDIATED SYSTEM

The novel bradykinin (BK) analog, RMP-7, was characterized in a series of in vitro tests to establish its selectivity as a B2 agonist. It wa s then used to study bradykinin's role in permeabilizing the blood bra in barrier (BBB) and blood brain-tumor barrier (BTB), using an RG2 rat glioma model. These studies demonstrated that: (1) B2 receptor stimul ation permeabilizes both the BBB and BTB in a dose-related fashion wit h greater effects observed in brain tumor-associated tissue, (2) the i ncreased permeability is sensitive, rapid and transient, and (3) tachy phylaxis occurs with continuous agonist administration, suggesting aut oregulation of the system's effects. These data therefore support the existence of a sophisticated. responsive and tightly regulated BK syst em whose activity modulates the permeability of the BBB.