Expression and function of bradykinin receptors in microglia

Expression of bradykinin (BK) receptors and their cellular function were investigated in microglia. Microglial cells were isolated from mixed cultures of cerebrocortical cells from postnatal day 3 Wistar rats. Reverse transcription-PCR (RT-PCR) showed that rat primary microglia express mRNAs for the type 2 bradykinin (B₂) receptor subtype but not the type 1 (B₁) receptor subtype under our experimental condition. However, the expression of B₁ receptor was greatly up-regulated after the treatment of microglia with BK for 24 hours. The expression of B₂ receptor in microglia was further confirmed by immunocytochemistry. Membrane currents were measured using whole-cell recording under voltage-clamp conditions. In 14% of patched cells (12/85 cells), BK (100-200 nM) induced an outward current at the holding potential of -20 mV, with oscillations in 2 cases. The BK-induced outward current was transient and desensitized rapidly. TEA inhibited the BK-induced outward current in a dose-dependent manner. These results suggest that microglia express B₂ receptors and presumably increase the intracellular Ca²⁺ concentration via inositol trisphosphate with the subsequent activation of Ca²⁺-dependent K⁺ channels. Our data provide the first evidence that microglia express functional BK receptors and support the idea that microglia play an important role in CNS inflammatory responses.