Neuropharmacology

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

Abstract

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 × 10−7mol/L), a selective B2 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 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.

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Correspondence to Wang-ping Hu.

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Hu, Wp., Li, Xm., Wu, Jl. et al. Bradykinin potentiates 5-HT3 receptor-mediated current in rat trigeminal ganglion neurons. Acta Pharmacol Sin 26, 428–434 (2005). https://doi.org/10.1111/j.1745-7254.2005.00074.x

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Keywords

  • bradykinin
  • 5-HT3 serotonin receptor
  • regulation
  • patch-clamp techniques
  • trigeminal ganglion

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