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Acta Pharmacologica Sinica 2005 Apr; 26 (4): 428-434; doi: 10.1111/j.1745-7254.2005.00074.x |
| Original Article | [ Full text ] |
| Bradykinin potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons |
| Wang-ping Hu1,2, Xue-mei Li2,
Ji-liang Wu3, Min Zheng3, Zhi-wang Li4 2Department of Physiology, 3Department of Pharmacology, Xianning College, Xianning 437100, China; 4Department of Neurobiology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China |
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Aim: To explore the modulatory effect of bradykinin (BK) on 5-HT3 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 (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 (1×10-6 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 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 EC50 value (19.1±3.2 µmol/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 of I5-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 mmol/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 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. |
Keywords: bradykinin; 5-HT3 serotonin receptor; regulation; patch-clamp techniques; trigeminal ganglion |
| 1 Correspondence to Prof Wang-ping Hu. Phn 86-715-826-0754. Email huwangping@21cn.com Received 2004-10-29 Accepted 2004-12-09 |
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