Open AccessBradykinin potentiates 5‐HT 3 receptor‐mediated current in rat trigeminal ganglion neurons
Author(s) -
HU Wangping,
LI Xuemei,
WU Jiliang,
ZHENG Min,
LI Zhiwang
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00074.x
Subject(s) - trigeminal ganglion , bradykinin , receptor , ganglion , neuroscience , chemistry , pharmacology , endocrinology , medicine , biology , sensory system
Aim : To explore the modulatory effect of bradykinin (BK) on 5‐HT 3 receptor‐mediated current in trigeminal ganglion (TG) neurons in rats. Methods : The whole‐cell patch‐clamp technique was used to record 5‐HT‐activated currents (I 5‐HT ) m 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‐HT 3 receptor antagonist, ICS‐205,930 (1 × 10 −6 mol/L). In 66 of the 74 cells sensitive to 5‐HT (89.2%), pretreatment for 30 s with BK (1 × 10 −6 ‐1 × 10 −10 mol/L) could potentiate I 5‐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 EC50 value (19.1±3.2 μmol/L vs 20.9±3.5 μmol/L; t‐test, P>0.05; n=8). BK potentiated I 5‐HT in a holding potential‐independent manner and did not alter the reverse potential of I 5‐HT . This BK‐induced potentiation of I 5‐HT was almost completely blocked by Hoe 140 (5 × 10 −7 mol/L), a selective B 2 BK receptor 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 I 5‐HT via a PKC‐dependent pathway in rat TG neurons, which may explain the peripheral mechanism of pain and hyperalgesia caused by, for example, tissue damage and inflammation.