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Human nicotinic receptors in chromaffin cells: characterization and pharmacology

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Abstract

During the last 10 years, we have been working on human chromaffin cells obtained from the adrenal gland of organ donors that suffered encephalic or cardiac death. We first electrophysiologically characterized the nicotinic acetylcholine receptors (nAChRs) activated by acetylcholine, and their contribution to the exocytosis of chromaffin vesicles and release of catecholamines. We have shown that these cells possess an adrenergic phenotype. This phenotype may contribute to an increased expression of α7 nAChRs in these cells, allowing for recording of α7 nAChR currents, something that had previously not been achieved in non-human species. The use of α-conotoxins allowed us to characterize non-α7 nAChR subtypes and, together with molecular biology experiments, conclude that the predominant nAChR subtype in human chromaffin cells is α3β4* (asterisk indicates the posible presence of additional subunits). In addition, there is a minor population of αxβ2 nAChRs. Both α7 and non-α7 nAChR subtypes contribute to the exocytotic process. Exocytosis mediated by nAChRs could be as large in magnitude as that elicited by calcium entry through voltage-dependent calcium channels. Finally, we have also investigated the effect of nAChR-targeted tobacco cessation drugs on catecholamine release in chromaffin cells. We have concluded that at therapeutic concentrations, varenicline alone does not increase the frequency of action potentials evoked by ACh. However, varenicline in the presence of nicotine does increase this frequency, and thus, in the presence of both drugs, the probability of increased catecholamine release in human chromaffin cells is high.

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Acknowledgements

This review is devoted to Prof. Antonio García, for his fervor and dedication to scientific research. And all anonymous organ donors and their families, for their generosity and collaboration in our scientific work.

Funding

This work was supported by grants from the Spanish Government (BFU2005-00743, BFU2008-01382/BFI, BFU2011-27690 to A.A.), the Spanish Ministerio de Economía, Industria y Competitividad (BFU2012-30997 and BFU2015-69092 to A.A.), the European Research Agency (NRHACC-329956 to A.A.), and the US National Institutes of Health (GM48677 and GM103801 to J.M.M).

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Authors and Affiliations

  1. Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Calle Arzobispo Morcillo 4, 28029, Madrid, Spain

    Almudena Albillos

  2. George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT, USA

    J. Michael McIntosh

  3. Department of Biology, University of Utah, Salt Lake City, UT, USA

    J. Michael McIntosh

  4. Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

    J. Michael McIntosh

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  1. Almudena Albillos
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  2. J. Michael McIntosh
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Correspondence to Almudena Albillos.

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This article is part of the special issue on Chromaffin Cells in Pflügers Archiv—European Journal of Physiology

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Albillos, A., McIntosh, J.M. Human nicotinic receptors in chromaffin cells: characterization and pharmacology. Pflugers Arch - Eur J Physiol 470, 21–27 (2018). https://doi.org/10.1007/s00424-017-2073-0

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  • DOI: https://doi.org/10.1007/s00424-017-2073-0

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