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Characterization of A-425619 at native TRPV1 receptors: a comparison between dorsal root ganglia and trigeminal ganglia.
Eur J Pharmacol. 2008 Oct 31; 596(1-3):62-9.EJ

Abstract

1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea (A-425619), a novel, potent, and selective transient receptor potential type V1 (TRPV1) antagonist, attenuates pain associated with inflammation and tissue injury in rats. The purpose of this study was to extend the in vitro characterization of A-425619 to native TRPV1 receptors and to compare the pharmacological properties of TRPV1 receptors in the dorsal root ganglion with trigeminal ganglion neurons. A robust increase in intracellular Ca(2+) was elicited by a variety of TRPV1 agonists with similar rank order of potency between both cultures: resiniferatoxin>tinyatoxin>capsaicin>N-arachidonoyl-dopamine (NADA). A-425619 blocked the 500 nM capsaicin response in both dorsal root ganglion with trigeminal ganglion cultures with IC(50) values of 78 nM and 115 nM, respectively, whereas capsazepine was significantly less potent (dorsal root ganglia: IC(50)=2.63 microM; trigeminal ganglia: IC(50)=6.31 microM). Furthermore, A-425619 was more potent in blocking the 3 microM NADA-evoked response in both dorsal root ganglia (IC(50)=36 nM) and trigeminal ganglia (IC(50)=37 nM) than capsazepine (dorsal root ganglia, IC(50)=741 nM; trigeminal ganglia, IC(50)=708 nM). Electrophysiology studies showed that 100 nM A-425619 completely inhibited TRPV1-mediated acid activated currents in dorsal root ganglia and trigeminal ganglia neurons. In addition, A-425619 blocked capsaicin- and NADA-evoked calcitonin gene-related peptide (CGRP) release in both cultures more effectively than capsazepine. These data show that A-425619 is a potent TRPV1 antagonist at the native TRPV1 receptors, and suggest that the pharmacological profile for TRPV1 receptors on dorsal root ganglia and trigeminal ganglia is very similar.

Authors+Show Affiliations

Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18755179

Citation

McDonald, Heath A., et al. "Characterization of A-425619 at Native TRPV1 Receptors: a Comparison Between Dorsal Root Ganglia and Trigeminal Ganglia." European Journal of Pharmacology, vol. 596, no. 1-3, 2008, pp. 62-9.
McDonald HA, Neelands TR, Kort M, et al. Characterization of A-425619 at native TRPV1 receptors: a comparison between dorsal root ganglia and trigeminal ganglia. Eur J Pharmacol. 2008;596(1-3):62-9.
McDonald, H. A., Neelands, T. R., Kort, M., Han, P., Vos, M. H., Faltynek, C. R., Moreland, R. B., & Puttfarcken, P. S. (2008). Characterization of A-425619 at native TRPV1 receptors: a comparison between dorsal root ganglia and trigeminal ganglia. European Journal of Pharmacology, 596(1-3), 62-9. https://doi.org/10.1016/j.ejphar.2008.07.063
McDonald HA, et al. Characterization of A-425619 at Native TRPV1 Receptors: a Comparison Between Dorsal Root Ganglia and Trigeminal Ganglia. Eur J Pharmacol. 2008 Oct 31;596(1-3):62-9. PubMed PMID: 18755179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of A-425619 at native TRPV1 receptors: a comparison between dorsal root ganglia and trigeminal ganglia. AU - McDonald,Heath A, AU - Neelands,Torben R, AU - Kort,Michael, AU - Han,Ping, AU - Vos,Melissa H, AU - Faltynek,Connie R, AU - Moreland,Robert B, AU - Puttfarcken,Pamela S, Y1 - 2008/08/05/ PY - 2008/04/09/received PY - 2008/07/18/revised PY - 2008/07/24/accepted PY - 2008/8/30/pubmed PY - 2009/1/13/medline PY - 2008/8/30/entrez SP - 62 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 596 IS - 1-3 N2 - 1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea (A-425619), a novel, potent, and selective transient receptor potential type V1 (TRPV1) antagonist, attenuates pain associated with inflammation and tissue injury in rats. The purpose of this study was to extend the in vitro characterization of A-425619 to native TRPV1 receptors and to compare the pharmacological properties of TRPV1 receptors in the dorsal root ganglion with trigeminal ganglion neurons. A robust increase in intracellular Ca(2+) was elicited by a variety of TRPV1 agonists with similar rank order of potency between both cultures: resiniferatoxin>tinyatoxin>capsaicin>N-arachidonoyl-dopamine (NADA). A-425619 blocked the 500 nM capsaicin response in both dorsal root ganglion with trigeminal ganglion cultures with IC(50) values of 78 nM and 115 nM, respectively, whereas capsazepine was significantly less potent (dorsal root ganglia: IC(50)=2.63 microM; trigeminal ganglia: IC(50)=6.31 microM). Furthermore, A-425619 was more potent in blocking the 3 microM NADA-evoked response in both dorsal root ganglia (IC(50)=36 nM) and trigeminal ganglia (IC(50)=37 nM) than capsazepine (dorsal root ganglia, IC(50)=741 nM; trigeminal ganglia, IC(50)=708 nM). Electrophysiology studies showed that 100 nM A-425619 completely inhibited TRPV1-mediated acid activated currents in dorsal root ganglia and trigeminal ganglia neurons. In addition, A-425619 blocked capsaicin- and NADA-evoked calcitonin gene-related peptide (CGRP) release in both cultures more effectively than capsazepine. These data show that A-425619 is a potent TRPV1 antagonist at the native TRPV1 receptors, and suggest that the pharmacological profile for TRPV1 receptors on dorsal root ganglia and trigeminal ganglia is very similar. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18755179/Characterization_of_A_425619_at_native_TRPV1_receptors:_a_comparison_between_dorsal_root_ganglia_and_trigeminal_ganglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00835-2 DB - PRIME DP - Unbound Medicine ER -