Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in the rat

Angelika Varga, J. Németh, Árpád Szabó, Jason J. McDougall, Chunfen Zhang, K. Elekes, E. Pintér, J. Szolcsányi, Z. Helyes

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

The TRPV1 capsaicin receptor is a non-selective cation channel localized in the cell membrane of a subset of primary sensory neurons and functions as an integrator molecule in nociceptive/inflammatory processes. The present paper characterizes the effects of SB366791, a novel TRPV1 antagonist, on capsaicin-evoked responses both in vitro and in vivo using rat models. SB366791 (100 and 500 nM) significantly inhibited capsaicin-evoked release of the pro-inflammatory sensory neuropeptide substance P from isolated tracheae, while it did not influence electrically induced neuropeptide release. It also decreased capsaicin-induced Ca2+ influx in cultured trigeminal ganglion cells in a concentration-dependent manner (0.5-10 μM) with an IC50 of 651.9 nM. In vivo 500 μg/kg i.p. dose of SB366791 significantly inhibited capsaicin-induced hypothermia, wiping movements and vasodilatation in the knee joint, while 2 mg/kg capsazepine was ineffective, its effect lasted for 1 h. However, neither antagonist was able to inhibit capsaicin-evoked hypothermia in Balb/c mice. Based on these data SB366791 is a more selective and in vivo also a more potent TRPV1 receptor antagonist than capsazepine in the rat therefore, it may promote the assessment of the therapeutic utility of TRPV1 channel blockers.

Original languageEnglish
Pages (from-to)137-142
Number of pages6
JournalNeuroscience Letters
Volume385
Issue number2
DOIs
Publication statusPublished - Sep 9 2005

Fingerprint

Capsaicin
Neuropeptides
TRPV Cation Channels
Induced Hypothermia
Trigeminal Ganglion
Sensory Receptor Cells
Substance P
Knee Joint
Trachea
Hypothermia
Vasodilation
Inhibitory Concentration 50
Cations
Cell Membrane
N-(3-methoxyphenyl)-4-chlorocinnamanilide
TRPV1 receptor
In Vitro Techniques
capsazepine

Keywords

  • Ca imaging
  • Hypothermia
  • Knee joint vasodilatation
  • SB366791
  • Substance P release
  • TRPV1 receptor antagonist
  • Wiping test

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in the rat. / Varga, Angelika; Németh, J.; Szabó, Árpád; McDougall, Jason J.; Zhang, Chunfen; Elekes, K.; Pintér, E.; Szolcsányi, J.; Helyes, Z.

In: Neuroscience Letters, Vol. 385, No. 2, 09.09.2005, p. 137-142.

Research output: Contribution to journalArticle

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