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

Neurosci Lett. 2004 Jul 22;365(2):147-52. doi: 10.1016/j.neulet.2004.04.072.

Abstract

The present study aimed to investigate the interaction between the coexistent SP receptor and 5-HT3 receptor in trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The majority of the neurons examined responded to 5-HT with an inward current (I5-HT) (78.2%, 79/101) that could be blocked by 5-HT3 receptor antagonist, ICS-205,930. The I5-HT was potentiated by preapplication of SP (10(-10) to 10(-8) M) in most 5-HT-sensitive cells(78.5%, 62/79). Coapplication of SP and GR-82334, antagonist of NK1 receptor, had no enhancing effect on I5-HT. The concentration-response curves for 5-HT with and without SP preapplication show that: (1) the threshold 5-HT concentrations with and without SP preapplication are basically the same, while SP preapplication increased the maximal value of I5-HT by 38.0% of its control; (2) the EC50 values of the curves with and without SP pretreatment are very close, i.e. 1.89 x 10(-5) M and 2.08 x 10(-5) M (P > 0.1; n = 9), respectively. Intracellular dialysis of GDP-beta-S, a non-hydrolyzable GDP analog, and GF-109203X, a selective protein kinase C inhibitor, removed the SP potentiation of I5-HT. These results may offer a clue to understanding the mechanism underlying the generation and/or regulation of peripheral pain caused by tissue damage inflammation, etc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Synergism
  • In Vitro Techniques
  • Neurokinin-1 Receptor Antagonists
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Cross-Talk
  • Receptors, Neurokinin-1 / physiology*
  • Receptors, Serotonin, 5-HT3 / physiology*
  • Serotonin Antagonists / pharmacology
  • Substance P / pharmacology
  • Substance P / physiology*
  • Trigeminal Ganglion / cytology
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / physiology*

Substances

  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-1
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Substance P