Pharmacological characterization of the TRPV1 receptor antagonist JYL1421 (SC0030) in vitro and in vivo in the rat.
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.
Jakab
Balázs
B
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7643, Pécs, Szigeti u. 12, Hungary.
Helyes
Zsuzsanna
Z
Varga
Angelika
A
Bölcskei
Kata
K
Szabó
Arpád
A
Sándor
Katalin
K
Elekes
Krisztián
K
Börzsei
Rita
R
Keszthelyi
Dániel
D
Pintér
Erika
E
Petho
Gábor
G
Németh
József
J
Szolcsányi
János
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D050916:TRPV Cation Channels; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D007473:Ion Channels; C466314:JYL 1421; D009479:Neuropeptides; D013449:Sulfonamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P; D013004:Somatostatin; D013890:Thiourea; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium