Pharmacological characterization of the TRPV1 receptor antagonist JYL1421 (SC0030) in vitro and in vivo in the rat
| Autor: | Zsuzsanna Helyes, Daniel Keszthelyi, Katalin Sándor, Kata Bölcskei, Rita Börzsei, Árpád Szabó, Gábor Petho, Balázs Jakab, József Németh, János Szolcsányi, Erika Pintér, Angelika Varga, Krisztián Elekes |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Calcitonin Gene-Related Peptide TRPV1 TRPV Cation Channels Blood Pressure Substance P In Vitro Techniques Calcitonin gene-related peptide Ion Channels Body Temperature chemistry.chemical_compound Trigeminal ganglion In vivo Internal medicine medicine Animals Elméleti orvostudományok Rats Wistar Receptor Neurons Pharmacology Sulfonamides Dose-Response Relationship Drug Neuropeptides Thiourea Antagonist Orvostudományok Electric Stimulation Rats Trachea Endocrinology chemistry Calcium lipids (amino acids peptides and proteins) Capsaicin Somatostatin Capsazepine |
| Zdroj: | European Journal of Pharmacology. 517:35-44 |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect