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

Autor: Lola Rueda-Ruzafa, José Medina-Polo, Carmen González-Enguita, Cristóbal de los Ríos, Sara Sanz-Lázaro, Arik J. Hone, Amanda Jiménez-Pompa, Almudena Albillos, Jesús Blázquez, J. Michael McIntosh
Přispěvatelé: UAM. Departamento de Farmacología
Rok vydání: 2021
Předmět:
0301 basic medicine
597) [Cytisine (PubChem CID]
Chromaffin Cells
Varenicline (PubChem CID:170361)
Nicotine
31762) [Dihydro-β-erythroidine (PubChem CID]
Nicotinic receptor
chemistry.chemical_compound
Catecholamines
0302 clinical medicine
1316) [Dimethylphenylpiperazinium (PubChem CID]
Adrenal Glands
Nicotinic Agonists
Nicotine (PubChem CID: 89594)
Varenicline
Adrenal gland
Chromaffin cell
Dihydro-β-erythroidine (PubChem CID: 31762)
medicine.anatomical_structure
Nicotinic agonist
Cytisine (PubChem CID: 597)
Acetylcholine
Human
medicine.drug
medicine.medical_specialty
Medicina
Dimethylphenylpiperazinium (PubChem CID: 1316)
89594) [Nicotine (PubChem CID]
Exocytosis
Acetylcholine (PubChem CID: 187)
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
medicine
Animals
Humans
Pharmacology
Rats
170361) [Varenicline (PubChem CID]
030104 developmental biology
Endocrinology
187) [Acetylcholine (PubChem CID]
chemistry
Catecholamine
Cattle
030217 neurology & neurosurgery
Zdroj: Biblos-e Archivo. Repositorio Institucional de la UAM
instname
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2021.108632
Popis: 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
This 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]
Databáze: OpenAIRE
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