Bradykinin potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons.
OBJECTIVE
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)) 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-HT(3 )receptor antagonist, ICS-205,930 (10(-6) mol/L). In 66 of the 74 cells sensitive to 5-HT (89.2%), pretreatment for 30 s with BK (10(-6)-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 EC(50) value (19.1+/-3.2 mumol/L vs 20.9+/-3.5 micromol/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 B2 BK receptor antagonist, and was removed after intracellular dialysis of GF-109203X (2 micromol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp.


CONCLUSIONS
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.
Hu
Wang-ping
WP
Department of Physiology, Xianning College, Xianning 437100, China. huwangping@21cn.com
Li
Xue-mei
XM
Wu
Ji-liang
JL
Zheng
Min
M
Li
Zhi-wang
ZW
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002469:Cell Separation; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists; D012668:Trigeminal Ganglion / Q000166:cytology / Q000502:physiology*; D000077526:Tropisetron
D065168:Bradykinin Receptor Antagonists; D007211:Indoles; D008301:Maleimides; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin; D000077526:Tropisetron; C065679:icatibant; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D001920:Bradykinin