Pharmacological characterization of the TRPV1 receptor antagonist JYL1421 (SC0030) in vitro and in vivo in the rat.

Abstract

The TRPV1 capsaicin receptor is an integrator molecule on primary afferent neurones participating in inflammatory and nociceptive processes. The present paper characterizes the effects of JYL1421 (SC0030), a TRPV1 receptor antagonist, on capsaicin-evoked responses both in vitro and in vivo in the rat. JYL1421 concentration-dependently (0.1-2 microM) inhibited capsaicin-evoked substance P, calcitonin gene-related peptide and somatostatin release from isolated tracheae, while only 2 microM resulted in a significant inhibition of electrically induced neuropeptide release. Capsazepine (0.1-2 microM), as a reference compound, similarly diminished both capsaicin-evoked and electrically evoked peptide release. JYL1421 concentration-dependently decreased capsaicin-induced Ca(2+) accumulation in cultured trigeminal ganglion cells, while capsazepine was much less effective. In vivo 2 mg/kg i.p. JYL1421, but not capsazepine, inhibited capsaicin-induced hypothermia, eye wiping movements and reflex hypotension (a component of the pulmonary chemoreflex or Bezold-Jarisch reflex). Based on these data JYL1421 is a more selective and in most models also a more potent TRPV1 receptor antagonist than capsazepine, therefore it may promote the assessment of the (patho)physiological roles of the TRPV1 receptor.

• Authors: Balázs Jakab, Zsuzsanna Helyes, Angelika Varga, Kata Bölcskei, Arpád Szabó, Katalin Sándor, Krisztián Elekes, Rita Börzsei, Dániel Keszthelyi, Erika Pintér, Gábor Petho, József Németh, János Szolcsányi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 517 Issue 1-2 Pg. 35-44 (Jul 04 2005) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15978575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ion Channels
• JYL 1421
• Neuropeptides
• Sulfonamides
• TRPV Cation Channels
• Trpv1 protein, rat
• Substance P
• Somatostatin
• Thiourea
• Calcitonin Gene-Related Peptide
• capsazepine
• Capsaicin
• Calcium

Topics

• Animals
• Blood Pressure (drug effects)
• Body Temperature (drug effects)
• Calcitonin Gene-Related Peptide (metabolism)
• Calcium (metabolism)
• Capsaicin (analogs & derivatives, pharmacology)
• Dose-Response Relationship, Drug
• Electric Stimulation
• In Vitro Techniques
• Ion Channels (antagonists & inhibitors, physiology)
• Male
• Neurons (drug effects, metabolism)
• Neuropeptides (metabolism)
• Rats
• Rats, Wistar
• Somatostatin (metabolism)
• Substance P (metabolism)
• Sulfonamides (pharmacology)
• TRPV Cation Channels
• Thiourea (analogs & derivatives, pharmacology)
• Trachea (drug effects, metabolism)