Nicotinic acetylcholine receptors of adrenal chromaffin cells
Abstract
In the adrenal medulla, acetylcholine released by the sympathetic splanchnic nerves activates neuronal-type nicotinic acetylcholine receptors (nAChRs) on the membrane of chromaffin cells which liberate catecholamines into the bloodstream in preparation for the fight and flight reactions. On adrenal chromaffin cells the main class of nAChRs is a pentameric assembly of alpha3 and beta4 subunits that forms ion channels which produce membrane depolarization by increasing Na+, K+ and Ca2+ permeability. Homomeric alpha7 nicotinic receptors are expressed in a species-dependent manner and do not contribute to catecholamine secretion. Chromaffin cell nAChRs rapidly activate and desensitize with full recovery on washout. nAChR activity is subjected to various types of dynamic regulation. It is allosterically modulated by the endogenous neuropeptide substance P that stabilizes receptors in their desensitized state, thus depressing their responsiveness. The full-length peptide CGRP acts as a negative allosteric modulator by inhibiting responses without changing desensitization, whereas its N-terminal fragments act as positive allosteric modulators to transiently enhance nAChR function. nAChR expression increases when cells are chronically exposed to either selective antagonists or agonists such as nicotine, a protocol mimicking the condition of chronic heavy smokers. In this case, large upregulation of nAChRs occurs even though most of the extra nAChRs remain inside the cells, creating a mismatch between the increase in total nAChRs and increase in functional nAChRs on the cell surface. These findings highlight the plastic properties of cholinergic neurotransmission in the adrenal medulla to provide robust mechanisms for adapting catecholamine release to acute and chronic changes in sympathetic activity.
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Adrenal chromaffin cells are classic neuroendocrine cells that secrete catecholamines upon receiving stimulation from sympathetic nerves.
“Adrenal chromaffin cells are classic neuroendocrine cells, which secrete catecholamines upon receiving stimulation from sympathetic nerves (Fenwick et al., 1982; Sala et al., 2008).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Sala et al., 2008
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- Authors
- Sala, F., Nistri, A., & Criado, M.
- Affiliations
- Instituto de Neurociencias (ES)
- Scuola Internazionale Superiore di Studi Avanzati (IT)
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2007-11-15
- Volume
- 192
- Issue
- 2
- Pages
- 203-212
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- OpenAlex
- W1546966740
- Cited by
- 90
- References
- 86
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 8 · 2013: 1 · 2012: 9
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- SDL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- nicotinic acetylcholine receptors, adrenal chromaffin cells, adrenal medulla, catecholamine release, α3β4 nAChR, alpha7 nAChR, receptor desensitization, substance P, calcitonin gene-related peptide, allosteric modulation, receptor up-regulation, nicotine, cholinergic neurotransmission, fight-or-flight response
- MeSH terms
- Acetylcholine, Animals, Cells, Cultured, Humans, Models, Biological, Neuronal Plasticity, Nicotine, Receptors, Nicotinic, Up-Regulation, Chromaffin Cells
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