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

Jiménez-Pompa, Amanda; Sanz-Lázaro, Sara; Hone, Arik J.; Rueda‐Ruzafa, Lola; Medina-Polo, J.; González-Enguita, C.; Blázquez, Jesús; Rı́os, Cristóbal de los; McIntosh, J. Michael; Albillos, Almudena

doi:10.1016/j.neuropharm.2021.108632

Cited by 2 publications

(2 citation statements)

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“…However, in Xenopus oocytes, Criado et al (2012) showed that stable and unstable interactions between a7 with b 4 or a3 subunits, respectively, were established among human and bovine receptor subunits. Here, we have shown that after maximal efficacy of activation of a7 and a3b nAChRs subtypes with the physiological agonist ACh, or by a synthetic agonist such as DMPP (Hone et al, 2017;Jiménez-Pompa et al, 2021), a sequence of events occurs. There is an increase of nAChR subtypes expression at the plasma membrane that are physically interacting and cooperating, and that become activatable and do not desensitize because of their mutual cooperation.…”

Section: Discussionmentioning

confidence: 99%

Cross Talk between α7 and α3β4 Nicotinic Receptors Prevents Their Desensitization in Human Chromaffin Cells

et al. 2021

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The physical interaction and functional cross talk among the different subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in the various tissues is unknown. Here, we have investigated this issue between the only two nAChRs subtypes expressed, the a7 and a3b4 subtypes, in a human native neuroendocrine cell (the chromaffin cell) using electrophysiological patch-clamp, fluorescence, and Förster resonance energy transfer (FRET) techniques. Our data show that a7 and a3b4 receptor subtypes require their mutual and maximal efficacy of activation to increase their expression, to avoid their desensitization, and therefore, to increase their activity. In this way, after repetitive stimulation with acetylcholine (ACh), a7 and a3b4 receptor subtypes do not desensitize, but they do with choline. The nicotinic current increase associated with the a3b4 subtype is dependent on Ca 21 . In addition, both receptor subtypes physically interact. Interaction and expression of both subtypes are reversibly reduced by tyrosine and serine/threonine phosphatases inhibition, not by Ca 21 . In addition, expression is greater in human chromaffin cells from men compared to women, but FRET efficiency is not affected. Together, our findings indicate that human a7 and a3b4 subtypes mutually modulate their expression and activity, providing a promising line of research to pharmacologically regulate their activity.

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Section: Discussionmentioning

confidence: 99%

Cross Talk between α7 and α3β4 Nicotinic Receptors Prevents Their Desensitization in Human Chromaffin Cells

et al. 2021

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“…Human adrenal chromaffin cells, for example, have enriched expression of α7 nAChRs and are involved in the stimulus-secretion coupling response [ 124 ]. Ligands that activate α7 nAChRs have been shown to be excitatory and increase catecholamine release from human chromaffin cells [ 125 , 126 ]. Such actions could increase plasma catecholamine levels and potentially trigger cardiovascular side effects.…”

Section: Discussionmentioning

confidence: 99%

Nicotinic acetylcholine receptors: Therapeutic targets for novel ligands to treat pain and inflammation

Hone

McIntosh

2023

Pharmacological Research

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

Cited by 2 publications

References 33 publications

Cross Talk between α7 and α3β4 Nicotinic Receptors Prevents Their Desensitization in Human Chromaffin Cells

Cross Talk between α7 and α3β4 Nicotinic Receptors Prevents Their Desensitization in Human Chromaffin Cells

Nicotinic acetylcholine receptors: Therapeutic targets for novel ligands to treat pain and inflammation

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