Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine

Cardiovascular side effects of varenicline and a case report of a hypertensive crisis in a varenicline-prescribed patient with pheochromocytoma have been reported. The goal of the present study was to determine whether such side effects might derive, in part, from increased exocytosis of secretory v...

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Autores: Jiménez-Pompa, Amanda, Sanz-Lázaro, Sara, Hone, Arik J., Rueda-Ruzafa, Lola, Medina-Polo, José, González Enguita, María del Carmen, Blázquez, Jesús, de los Ríos, Cristóbal, Michael McIntosh, J., Albillos Martínez, María Almudena
Tipo de documento: artigo
Data de publicação:2021
País:España
Recursos:IAPH
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/700516
Acesso em linha:http://hdl.handle.net/10486/700516
https://dx.doi.org/10.1016/j.neuropharm.2021.108632
Access Level:Acceso aberto
Palavra-chave:Acetylcholine (PubChem CID: 187)
Chromaffin cell
Cytisine (PubChem CID: 597)
Dihydro-β-erythroidine (PubChem CID: 31762)
Dimethylphenylpiperazinium (PubChem CID: 1316)
Exocytosis
Human
Nicotine
Nicotine (PubChem CID: 89594)
Nicotinic receptor
Varenicline
Varenicline (PubChem CID:170361)
Medicina
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spelling Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotineJiménez-Pompa, AmandaSanz-Lázaro, SaraHone, Arik J.Rueda-Ruzafa, LolaMedina-Polo, JoséGonzález Enguita, María del CarmenBlázquez, Jesúsde los Ríos, CristóbalMichael McIntosh, J.Albillos Martínez, María AlmudenaAcetylcholine (PubChem CID: 187)Chromaffin cellCytisine (PubChem CID: 597)Dihydro-β-erythroidine (PubChem CID: 31762)Dimethylphenylpiperazinium (PubChem CID: 1316)ExocytosisHumanNicotineNicotine (PubChem CID: 89594)Nicotinic receptorVareniclineVarenicline (PubChem CID:170361)MedicinaCardiovascular side effects of varenicline and a case report of a hypertensive crisis in a varenicline-prescribed patient with pheochromocytoma have been reported. The goal of the present study was to determine whether such side effects might derive, in part, from increased exocytosis of secretory vesicles and subsequent catecholamine release triggered by varenicline in human chromaffin cells of the adrenal gland. In this study, we performed electrophysiological plasma membrane capacitance and carbon fiber amperometry experiments to evaluate the effect of varenicline on exocytosis and catecholamine release, respectively, at concentrations reached during varenicline therapy (100 nM). Experiments were conducted in the absence or presence of nicotine, at plasma concentrations achieved right after smoking (250 nM) or steady-state concentrations (110 nM), in chromaffin cells of the adrenal gland obtained from human organ donors. Cells were stimulated with short pulses (10 ms) of acetylcholine (ACh; 300 μM) applied at 0.2 Hz, in order to closer mimic the physiological situation at the splanchnic nerve-chromaffin cell synapse. In addition, rat chromaffin cells were used to compare the effects obtained in cells from a more readily available species. Varenicline increased the exocytosis of secretory vesicles in human and rat chromaffin cells in the presence of nicotine, effects that were not due to an increase of plasma membrane capacitance or currents triggered by the nicotinic agonists alone. These results should be considered in nicotine addiction therapies when varenicline is usedThis work was supported by grants from the Spanish Ministry of Science and Innovation [grant number BFU2015-69092 to A.A.] and the U.S. National Institutes of Health [GM136430 and GM103801 to J.M.M]ElsevierDepartamento de FarmacologíaFacultad de Medicina20212021-06-04research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/700516https://dx.doi.org/10.1016/j.neuropharm.2021.108632reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:IAPHInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7005162026-06-23T12:46:27Z
dc.title.none.fl_str_mv Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
title Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
spellingShingle Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
Jiménez-Pompa, Amanda
Acetylcholine (PubChem CID: 187)
Chromaffin cell
Cytisine (PubChem CID: 597)
Dihydro-β-erythroidine (PubChem CID: 31762)
Dimethylphenylpiperazinium (PubChem CID: 1316)
Exocytosis
Human
Nicotine
Nicotine (PubChem CID: 89594)
Nicotinic receptor
Varenicline
Varenicline (PubChem CID:170361)
Medicina
title_short Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
title_full Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
title_fullStr Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
title_full_unstemmed Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
title_sort Therapeutic concentrations of varenicline increases exocytotic release of catecholamines from human and rat adrenal chromaffin cells in the presence of nicotine
dc.creator.none.fl_str_mv Jiménez-Pompa, Amanda
Sanz-Lázaro, Sara
Hone, Arik J.
Rueda-Ruzafa, Lola
Medina-Polo, José
González Enguita, María del Carmen
Blázquez, Jesús
de los Ríos, Cristóbal
Michael McIntosh, J.
Albillos Martínez, María Almudena
author Jiménez-Pompa, Amanda
author_facet Jiménez-Pompa, Amanda
Sanz-Lázaro, Sara
Hone, Arik J.
Rueda-Ruzafa, Lola
Medina-Polo, José
González Enguita, María del Carmen
Blázquez, Jesús
de los Ríos, Cristóbal
Michael McIntosh, J.
Albillos Martínez, María Almudena
author_role author
author2 Sanz-Lázaro, Sara
Hone, Arik J.
Rueda-Ruzafa, Lola
Medina-Polo, José
González Enguita, María del Carmen
Blázquez, Jesús
de los Ríos, Cristóbal
Michael McIntosh, J.
Albillos Martínez, María Almudena
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Farmacología
Facultad de Medicina
dc.subject.none.fl_str_mv Acetylcholine (PubChem CID: 187)
Chromaffin cell
Cytisine (PubChem CID: 597)
Dihydro-β-erythroidine (PubChem CID: 31762)
Dimethylphenylpiperazinium (PubChem CID: 1316)
Exocytosis
Human
Nicotine
Nicotine (PubChem CID: 89594)
Nicotinic receptor
Varenicline
Varenicline (PubChem CID:170361)
Medicina
topic Acetylcholine (PubChem CID: 187)
Chromaffin cell
Cytisine (PubChem CID: 597)
Dihydro-β-erythroidine (PubChem CID: 31762)
Dimethylphenylpiperazinium (PubChem CID: 1316)
Exocytosis
Human
Nicotine
Nicotine (PubChem CID: 89594)
Nicotinic receptor
Varenicline
Varenicline (PubChem CID:170361)
Medicina
description Cardiovascular side effects of varenicline and a case report of a hypertensive crisis in a varenicline-prescribed patient with pheochromocytoma have been reported. The goal of the present study was to determine whether such side effects might derive, in part, from increased exocytosis of secretory vesicles and subsequent catecholamine release triggered by varenicline in human chromaffin cells of the adrenal gland. In this study, we performed electrophysiological plasma membrane capacitance and carbon fiber amperometry experiments to evaluate the effect of varenicline on exocytosis and catecholamine release, respectively, at concentrations reached during varenicline therapy (100 nM). Experiments were conducted in the absence or presence of nicotine, at plasma concentrations achieved right after smoking (250 nM) or steady-state concentrations (110 nM), in chromaffin cells of the adrenal gland obtained from human organ donors. Cells were stimulated with short pulses (10 ms) of acetylcholine (ACh; 300 μM) applied at 0.2 Hz, in order to closer mimic the physiological situation at the splanchnic nerve-chromaffin cell synapse. In addition, rat chromaffin cells were used to compare the effects obtained in cells from a more readily available species. Varenicline increased the exocytosis of secretory vesicles in human and rat chromaffin cells in the presence of nicotine, effects that were not due to an increase of plasma membrane capacitance or currents triggered by the nicotinic agonists alone. These results should be considered in nicotine addiction therapies when varenicline is used
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-06-04
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/700516
https://dx.doi.org/10.1016/j.neuropharm.2021.108632
url http://hdl.handle.net/10486/700516
https://dx.doi.org/10.1016/j.neuropharm.2021.108632
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:IAPH
instname_str IAPH
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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