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

Aim:To explore the modulatory effect of bradykinin (BK) on 5-HT3receptor-mediated current in trigeminal ganglion (TG) neurons in rats.Methods:The whole-cell patch-clamp technique was used to record 5-HT-activated currents (I5-HT) inneurons freshly dissociated from rat TG.Drugs were applied by rapid solutionexchange.Results:The majority of the neurons examined responded to 5-HTapplied externally with an inward current (76.3%,74/97) that could be blocked bythe 5-HT3receptor antagonist,ICS-205,930 (1×10-6mol/L).In 66 of the 74 cellssensitive to 5-HT (89.2%),pretreatment for 30 s with BK (1×10-6-1×10-10mol/L)could potentiate I5-HTwith the maximal modulatory effect occurring at10-7mol/L BK (71.6%+4.9%).BK shifted the 5-HT concentration-response curveupwards with an increase of 68.9%±7.2% in the maximal current response,but withno significant change in the EC50value (19.1±3.2 μmol/L vs 20.9±3.5 μmol/L;t-test,P>0.05;n=8).BK potentiated I5-HTin a holding potential-independent manner anddid not alter the reverse potential of I5-HT.This BK-induced potentiation ofI5-HTwas almost completely blocked by Hoe 140 (5×10-7mol/L),a selective B2BKreceptor 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-HTvia a PKC-dependent pathway in rat TG neurons,which may explain the peripheral’mecha-nism of pain and hyperalgesia caused by,for example,tissue damage andinflammation.