Bradykinin potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons

摘要

Aim: To explore the modulatory effect of bradykinin (BK) on 5-HT3 receptormediated current in trigeminal ganglion (TG) neurons in rats. Methods: The wholecell patch-clamp technique was used to record 5-HT-activated currents (I5-HT) in neurons freshly dissociated from rat TG. Drugs were applied by rapid solution exchange. Results: The majority of the neurons examined responded to 5-HT applied externally with an inward current (76.3%, 74/97) that could be blocked by the 5-HT3 receptor antagonist, ICS-205,930 (1×10-6mol/L). In 66 of the 74 cells sensitive to 5-HT (89.2%), pretreatment for 30 s with BK (1x 10-6-1× 10-10 mol/L) could potentiate I5-HT with the maximal modulatory effect occurring at 10-7 mol/L BK (71.6%±4.9%). BK shifted the 5-HT concentration-response curve upwards with an increase of 68.9%±7.2% in the maximal current response, but with no significant change in the ECs0 value (19.1±3.2 μmool/L vs 20.9±3.5 μmol/L; t-test, P＞0.05; n=8). BK potentiated I5-HT in a holding potential-independent manner and did not alter the reverse potential of I5-HT. This BK-induced potentiation ofI5-HT was almost completely blocked by Hoe 140 (5x 10-7 mol/L), a selective B2 BKreceptor antagonist, and was removed after intracellular dialysis of GF-109203X (2 μmol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. Conclusion: Pre-application of BK exerts an enhancing effect on I5-HT via a PKCdependent pathway in rat TG neurons, which may explain the peripheral mechanism of pain and hyperalgesia caused by, for example, tissue damage and infammation.