Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in the rat.
Neurosci Lett
; 385(2): 137-42, 2005 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-15950380
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 microM) with an IC50 of 651.9 nM. In vivo 500 microg/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 1h. 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Nociceptores
/
Cinamatos
/
Sistema Nervoso Periférico
/
Canais Iônicos
/
Anilidas
/
Neurônios Aferentes
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article