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TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs

We examined the molecular pharmacology and in vivo effects of a TRPV1 receptor antagonist, N-(4-Tertiarybutylphenyl)-4(3-cholorphyridin-2-yl)-tetrahydro-pyrazine1(2H) – carboxamide (BCTC) on the guinea pig TRPV1 cation channel. BCTC antagonized capsaicin-induced activation and PMA-mediated activatio...

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Autores principales: McLeod, Robbie L, Fernandez, Xiomara, Correll, Craig C, Phelps, Tara P, Jia, Yanlin, Wang, Xin, Hey, John A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764418/
https://www.ncbi.nlm.nih.gov/pubmed/17173683
http://dx.doi.org/10.1186/1745-9974-2-10
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author McLeod, Robbie L
Fernandez, Xiomara
Correll, Craig C
Phelps, Tara P
Jia, Yanlin
Wang, Xin
Hey, John A
author_facet McLeod, Robbie L
Fernandez, Xiomara
Correll, Craig C
Phelps, Tara P
Jia, Yanlin
Wang, Xin
Hey, John A
author_sort McLeod, Robbie L
collection PubMed
description We examined the molecular pharmacology and in vivo effects of a TRPV1 receptor antagonist, N-(4-Tertiarybutylphenyl)-4(3-cholorphyridin-2-yl)-tetrahydro-pyrazine1(2H) – carboxamide (BCTC) on the guinea pig TRPV1 cation channel. BCTC antagonized capsaicin-induced activation and PMA-mediated activation of guinea pig TRPV1 with IC(50 )values of 12.2 ± 5.2 nM, and 0.85 ± 0.10 nM, respectively. In addition, BCTC (100 nM) completely blocked the ability of heterologously expressed gpTRPV1 to respond to decreases in pH. Thus, BCTC is able to block polymodal activation of gpTRPV1. Furthermore, in nodose ganglia cells, capsaicin induced Ca(2+ )influx through TRPV1 channel was inhibited via BCTC in a concentration dependent manner. In in vivo studies capsaicin (10 – 300 μM) delivered by aerosol to the pulmonary system of non-sensitized guinea pigs produced an increase in cough frequency. In these studies, the tussigenic effects of capsaicin (300 μM) were blocked in a dose dependent fashion when BCTC (0.01–3.0 mg/kg, i.p.) was administered 30 minutes before challenge. The high dose of BCTC (3.0 mg/kg, i.p) produced a maximum inhibition of capsaicin-induced cough of 65%. We also studied the effects of BCTC (0.03 and 3.0) when administered 60 minutes before capsaicin. Under these conditions, BCTC (3.0 mg/kg, i.p) produced a maximum decrease in capsaicin-induced cough of 31%. In ovalbumin passively sensitized guinea pigs, we found that BCTC (1 and 3 mg/kg, i.p.) attenuated antigen ovalbumin (0.3%) cough responses by 27% and 60%, respectively. We conclude that TRPV1 channel activation may play role in cough mediated by antigen in sensitized guinea pigs. Our results supports increasing evidence that TRPV1 may play a role in the generation of the cough response.
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spelling pubmed-17644182007-01-06 TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs McLeod, Robbie L Fernandez, Xiomara Correll, Craig C Phelps, Tara P Jia, Yanlin Wang, Xin Hey, John A Cough Research We examined the molecular pharmacology and in vivo effects of a TRPV1 receptor antagonist, N-(4-Tertiarybutylphenyl)-4(3-cholorphyridin-2-yl)-tetrahydro-pyrazine1(2H) – carboxamide (BCTC) on the guinea pig TRPV1 cation channel. BCTC antagonized capsaicin-induced activation and PMA-mediated activation of guinea pig TRPV1 with IC(50 )values of 12.2 ± 5.2 nM, and 0.85 ± 0.10 nM, respectively. In addition, BCTC (100 nM) completely blocked the ability of heterologously expressed gpTRPV1 to respond to decreases in pH. Thus, BCTC is able to block polymodal activation of gpTRPV1. Furthermore, in nodose ganglia cells, capsaicin induced Ca(2+ )influx through TRPV1 channel was inhibited via BCTC in a concentration dependent manner. In in vivo studies capsaicin (10 – 300 μM) delivered by aerosol to the pulmonary system of non-sensitized guinea pigs produced an increase in cough frequency. In these studies, the tussigenic effects of capsaicin (300 μM) were blocked in a dose dependent fashion when BCTC (0.01–3.0 mg/kg, i.p.) was administered 30 minutes before challenge. The high dose of BCTC (3.0 mg/kg, i.p) produced a maximum inhibition of capsaicin-induced cough of 65%. We also studied the effects of BCTC (0.03 and 3.0) when administered 60 minutes before capsaicin. Under these conditions, BCTC (3.0 mg/kg, i.p) produced a maximum decrease in capsaicin-induced cough of 31%. In ovalbumin passively sensitized guinea pigs, we found that BCTC (1 and 3 mg/kg, i.p.) attenuated antigen ovalbumin (0.3%) cough responses by 27% and 60%, respectively. We conclude that TRPV1 channel activation may play role in cough mediated by antigen in sensitized guinea pigs. Our results supports increasing evidence that TRPV1 may play a role in the generation of the cough response. BioMed Central 2006-12-15 /pmc/articles/PMC1764418/ /pubmed/17173683 http://dx.doi.org/10.1186/1745-9974-2-10 Text en Copyright © 2006 McLeod et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
McLeod, Robbie L
Fernandez, Xiomara
Correll, Craig C
Phelps, Tara P
Jia, Yanlin
Wang, Xin
Hey, John A
TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title_full TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title_fullStr TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title_full_unstemmed TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title_short TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
title_sort trpv1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764418/
https://www.ncbi.nlm.nih.gov/pubmed/17173683
http://dx.doi.org/10.1186/1745-9974-2-10
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