Lack of evidence for functional TRPV1 vanilloid receptors in rat hippocampal nerve terminals

Neurosci Lett. 2006 Jul 31;403(1-2):151-6. doi: 10.1016/j.neulet.2006.04.030. Epub 2006 May 2.


Although TRPV(1) vanilloid receptors (TRPV(1)Rs) have been assumed to be present in the brain, their role is not well-defined. Here, we tested the widely used TRPV(1)R agonists (E)-capsaicin (0.1-100 microM) and resiniferatoxin (RTX, 0.1 microM) on resting and K(+)-evoked Ca(2+) entry and radiolabelled GABA release in rat hippocampal nerve terminals. (E)-capsaicin and RTX failed to evoke Ca(2+) transients or to trigger [(3)H]GABA outflow. Both (E)-capsaicin (EC(50), 40.4 microM) and its enantiomer (Z)-capsaicin (EC(50), 22.9 microM), which is inactive at the TRPV(1)R, inhibited the K(+)-evoked Ca(2+) entry, and to similar extent, the Ca(2+)-dependent K(+)-evoked [(3)H]GABA release. The TRPV(1)R enhancer/partial agonist 2-aminoethoxydiphenyl borate (1-300 microM) induced rapid Ca(2+) entry. None of the above-mentioned findings proved to be sensitive to the TRPV(1)R antagonists iodoresiniferatoxin (I-RTX; 3 microM) and SB366791 (3 microM). The CB(1) cannabinoid receptor antagonist AM251 (EC(50), 1.1 microM) and I-RTX (EC(50), 4.6 microM) also diminished the K(+)-evoked Ca(2+) entry per se. We observed competitive antagonism between I-RTX and AM251, indicating that the two molecules may act at the same site. In conclusion, there is a need to examine the discrepancy between ex vivo and in vitro data to understand the neurochemical and physiological functions of brain TRPV(1)Rs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Capsaicin / pharmacology
  • Diterpenes / pharmacology
  • Fluorometry
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Male
  • Potassium / metabolism
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Wistar
  • Stereoisomerism
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • Diterpenes
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • gamma-Aminobutyric Acid
  • resiniferatoxin
  • Potassium
  • Capsaicin
  • Calcium