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Alpha2-adrenoceptors in adrenomedullary chromaffin cells: functional role and pathophysiological implications

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Abstract

Chromaffin cells from the adrenal medulla participate in stress responses by releasing catecholamines into the bloodstream. Main control of adrenal catecholamine secretion is exerted both neurally (by the splanchnic nerve fibers) and humorally (by corticosteroids, circulating noradrenaline, etc.). It should be noted, however, that secretory products themselves (catecholamines, ATP, opioids, ascorbic acid, chromogranins) could also influence the secretory response in an autocrine/paracrine manner. This form of control is activity-dependent and can be either inhibitory or excitatory. Among the inhibitory influences, it stands out the one mediated by α2-adrenergic autoreceptors activated by released catecholamines. α2-adrenoceptors are G protein-coupled receptors capable to inhibit exocytotic secretion through a direct interaction of Gβγ subunits with voltage-gated Ca2+ channels. Interestingly, upon intense and/or prolonged stimulation, α2-adrenergic receptors become desensitized by the intervention of G protein-coupled receptor kinase 2 (GRK2). In several experimental models of heart failure, there has been reported the up-regulation of GRK2 and the loss of functioning of inhibitory α2-adrenoceptors resulting in enhanced release of adrenomedullary catecholamines. Given the importance of circulating catecholamines in the pathophysiology of heart failure, the recovery of α2-adrenergic modulation of the secretory response from chromaffin cells appears as a novel strategy for a better control of the patients with this cardiac disease.

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Acknowledgements

The authors would like to thank Professor Antonio G. García for his teaching, mentorship, and continuous support over more than 30 years.

Funding information

Funding from the Spanish Government (grant Ref. No. BFU2011-26253; BFU2015-70067-REDC) and Comunidad de Madrid (BRADE-CM S2013/ICE-2958) is greatly appreciated.

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Authors and Affiliations

  1. Institute for Research in Neurochemistry & Department of Toxicology and Pharmacology, Faculty of Veterinary, Universidad Complutense de Madrid, Avda. Puerta de Hierro s/n, 28029, Madrid, Spain

    Antonio R. Artalejo & Luis Alcides Olivos-Oré

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  1. Antonio R. Artalejo
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  2. Luis Alcides Olivos-Oré
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Correspondence to Antonio R. Artalejo.

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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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Artalejo, A.R., Olivos-Oré, L.A. Alpha2-adrenoceptors in adrenomedullary chromaffin cells: functional role and pathophysiological implications. Pflugers Arch - Eur J Physiol 470, 61–66 (2018). https://doi.org/10.1007/s00424-017-2059-y

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  • DOI: https://doi.org/10.1007/s00424-017-2059-y

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