Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Expression of α3β2β4 nicotinic acetylcholine receptors by rat adrenal chromaffin cells determined using novel conopeptide antagonists.
Hone AJ
,
Rueda-Ruzafa L
,
Gordon TJ
,
Gajewiak J
,
Christensen S
,
Dyhring T
,
Albillos A
,
McIntosh JM
.
???displayArticle.abstract???
Adrenal chromaffin cells release neurotransmitters in response to stress and may be involved in conditions such as post-traumatic stress and anxiety disorders. Neurotransmitter release is triggered, in part, by activation of nicotinic acetylcholine receptors (nAChRs). However, despite decades of use as a model system for studying exocytosis, the nAChR subtypes involved have not been pharmacologically identified. Quantitative real-time PCR of rat adrenal medulla revealed an abundance of mRNAs for α3, α7, β2, and β4 subunits. Whole-cell patch-clamp electrophysiology of chromaffin cells and subtype-selective ligands were used to probe for nAChRs derived from the mRNAs found in adrenal medulla. A novel conopeptide antagonist, PeIA-5469, was created that is highly selective for α3β2 over other nAChR subtypes heterologously expressed in Xenopus laevis oocytes. Experiments using PeIA-5469 and the α3β4-selective α-conotoxin TxID revealed that rat adrenal medulla contain two populations of chromaffin cells that express either α3β4 nAChRs alone or α3β4 together with the α3β2β4 subtype. Conclusions were derived from observations that acetylcholine-gated currents in some cells were sensitive to inhibition by PeIA-5469 and TxID, while in other cells, currents were sensitive only to TxID. Expression of functional α7 nAChRs was determined using three α7-selective ligands: the agonist PNU282987, the positive allosteric modulator PNU120596, and the antagonist α-conotoxin [V11L,V16D]ArIB. The results of these studies identify for the first time the expression of α3β2β4 nAChRs as well as functional α7 nAChRs by rat adrenal chromaffin cells.
Albillos,
Human nicotinic receptors in chromaffin cells: characterization and pharmacology.
2018, Pubmed
Albillos,
Human nicotinic receptors in chromaffin cells: characterization and pharmacology.
2018,
Pubmed
Arribas-Blázquez,
Overexpression of P2X3 and P2X7 Receptors and TRPV1 Channels in Adrenomedullary Chromaffin Cells in a Rat Model of Neuropathic Pain.
2019,
Pubmed
Biales,
Electrical excitability of cultured adrenal chromaffin cells.
1976,
Pubmed
Bibevski,
Functional nicotinic acetylcholine receptors that mediate ganglionic transmission in cardiac parasympathetic neurons.
2000,
Pubmed
Bodnar,
Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors.
2005,
Pubmed
Brandt,
Action potentials in the rat chromaffin cell and effects of acetylcholine.
1976,
Pubmed
Broide,
Distribution of α7 Nicotinic Acetylcholine Receptor Subunit mRNA in the Developing Mouse.
2019,
Pubmed
Broxton,
Alpha-conotoxin ImI inhibits the alpha-bungarotoxin-resistant nicotinic response in bovine adrenal chromaffin cells.
1999,
Pubmed
Chatzidaki,
Pharmacological Characterisation of Nicotinic Acetylcholine Receptors Expressed in Human iPSC-Derived Neurons.
2015,
Pubmed
Ciuraszkiewicz,
Single-channel properties of α3β4, α3β4α5 and α3β4β2 nicotinic acetylcholine receptors in mice lacking specific nicotinic acetylcholine receptor subunits.
2013,
Pubmed
Coe,
Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation.
2005,
Pubmed
,
Xenbase
Colomer,
Functional characterization of alpha9-containing cholinergic nicotinic receptors in the rat adrenal medulla: implication in stress-induced functional plasticity.
2010,
Pubmed
Criado,
Differential expression of alpha-bungarotoxin-sensitive neuronal nicotinic receptors in adrenergic chromaffin cells: a role for transcription factor Egr-1.
1997,
Pubmed
Criado,
Acetylcholine nicotinic receptor subtypes in chromaffin cells.
2018,
Pubmed
DOUGLAS,
The role of calcium in the secretory response of the adrenal medulla to acetylcholine.
1961,
Pubmed
Dani,
Neuronal Nicotinic Acetylcholine Receptor Structure and Function and Response to Nicotine.
2015,
Pubmed
David,
Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of nAChR subunit genes.
2010,
Pubmed
,
Xenbase
Di Angelantonio,
Molecular biology and electrophysiology of neuronal nicotinic receptors of rat chromaffin cells.
2003,
Pubmed
Douglas,
Stimulus-secretion coupling: the concept and clues from chromaffin and other cells.
1968,
Pubmed
Douglas,
Effects of acetylcholine and other medullary secretagogues and antagonists on the membrane potential of adrenal chromaffin cells: an analysis employing techniques of tissue culture.
1967,
Pubmed
Eiden,
What's New in Endocrinology: The Chromaffin Cell.
2018,
Pubmed
Eiden,
PACAP signaling in stress: insights from the chromaffin cell.
2018,
Pubmed
El-Hajj,
Pharmacological and immunological identification of native alpha7 nicotinic receptors: evidence for homomeric and heteromeric alpha7 receptors.
2007,
Pubmed
Fuentealba,
A choline-evoked [Ca2+]c signal causes catecholamine release and hyperpolarization of chromaffin cells.
2004,
Pubmed
,
Xenbase
Gahring,
Nicotinic receptor Alpha7 expression during mouse adrenal gland development.
2014,
Pubmed
García,
Calcium signaling and exocytosis in adrenal chromaffin cells.
2006,
Pubmed
Genzen,
Dorsal root ganglion neurons express multiple nicotinic acetylcholine receptor subtypes.
2001,
Pubmed
Gershon,
Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation.
2018,
Pubmed
Giribaldi,
α-Conotoxins to explore the molecular, physiological and pathophysiological functions of neuronal nicotinic acetylcholine receptors.
2018,
Pubmed
Hajós,
The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.
2005,
Pubmed
Hamelink,
Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis.
2002,
Pubmed
Harrison-Woolrych,
Cardiovascular events in patients taking varenicline: a case series from intensive postmarketing surveillance in New Zealand.
2012,
Pubmed
Hone,
Nicotinic acetylcholine receptors in dorsal root ganglion neurons include the α6β4* subtype.
2012,
Pubmed
Hone,
α-Conotoxins Identify the α3β4* Subtype as the Predominant Nicotinic Acetylcholine Receptor Expressed in Human Adrenal Chromaffin Cells.
2015,
Pubmed
,
Xenbase
Hone,
α-Conotoxin PeIA[S9H,V10A,E14N] potently and selectively blocks α6β2β3 versus α6β4 nicotinic acetylcholine receptors.
2012,
Pubmed
,
Xenbase
Hone,
Therapeutic concentrations of varenicline in the presence of nicotine increase action potential firing in human adrenal chromaffin cells.
2017,
Pubmed
,
Xenbase
Hone,
PeIA-5466: A Novel Peptide Antagonist Containing Non-natural Amino Acids That Selectively Targets α3β2 Nicotinic Acetylcholine Receptors.
2019,
Pubmed
,
Xenbase
Hone,
Positional scanning mutagenesis of α-conotoxin PeIA identifies critical residues that confer potency and selectivity for α6/α3β2β3 and α3β2 nicotinic acetylcholine receptors.
2013,
Pubmed
,
Xenbase
Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase
Kalappa,
Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.
2010,
Pubmed
Kanczkowski,
The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis.
2015,
Pubmed
Kuri,
PACAP regulates immediate catecholamine release from adrenal chromaffin cells in an activity-dependent manner through a protein kinase C-dependent pathway.
2009,
Pubmed
Lind,
Association of Posttraumatic Stress Disorder With rs2267735 in the ADCYAP1R1 Gene: A Meta-Analysis.
2017,
Pubmed
Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed
Livett,
Use of isolated chromaffin cells to study basic release mechanisms.
1983,
Pubmed
Luo,
Characterization of a novel α-conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors.
2013,
Pubmed
,
Xenbase
López,
Unmasking the functions of the chromaffin cell alpha7 nicotinic receptor by using short pulses of acetylcholine and selective blockers.
1998,
Pubmed
,
Xenbase
Mahapatra,
Calcium channel types contributing to chromaffin cell excitability, exocytosis and endocytosis.
2012,
Pubmed
Mao,
Heterogeneity of nicotinic cholinergic receptors in rat superior cervical and nodose Ganglia.
2006,
Pubmed
McIntosh,
Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors.
2004,
Pubmed
,
Xenbase
Mihalak,
Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors.
2006,
Pubmed
,
Xenbase
Mizobe,
Nicotine stimulates secretion of both catecholamines and acetylcholinesterase from cultured adrenal chromaffin cells.
1983,
Pubmed
Neher,
Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells.
1982,
Pubmed
Olsen,
Two distinct allosteric binding sites at α4β2 nicotinic acetylcholine receptors revealed by NS206 and NS9283 give unique insights to binding activity-associated linkage at Cys-loop receptors.
2013,
Pubmed
,
Xenbase
Pardi,
Pituitary adenylate cyclase-activating polypeptide activates a phospholipase C-dependent signal pathway in chick ciliary ganglion neurons that selectively inhibits alpha7-containing nicotinic receptors.
1999,
Pubmed
Podvin,
Profiles of secreted neuropeptides and catecholamines illustrate similarities and differences in response to stimulation by distinct secretagogues.
2015,
Pubmed
Pérez-Alvarez,
Key role of the nicotinic receptor in neurotransmitter exocytosis in human chromaffin cells.
2007,
Pubmed
Pérez-Alvarez,
Pharmacological and biophysical properties of Ca2+ channels and subtype distributions in human adrenal chromaffin cells.
2008,
Pubmed
Pérez-Alvarez,
Pharmacological characterization of native α7 nicotinic ACh receptors and their contribution to depolarization-elicited exocytosis in human chromaffin cells.
2012,
Pubmed
Rau,
Nicotinic AChR in subclassified capsaicin-sensitive and -insensitive nociceptors of the rat DRG.
2005,
Pubmed
Ressler,
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor.
2011,
Pubmed
Rollema,
Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence.
2010,
Pubmed
,
Xenbase
Sala,
Nicotinic acetylcholine receptors of adrenal chromaffin cells.
2008,
Pubmed
Singh,
Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis.
2011,
Pubmed
Smith,
Comparative functional expression of nAChR subtypes in rodent DRG neurons.
2013,
Pubmed
Stokes,
Use of an α3β4 nicotinic acetylcholine receptor subunit concatamer to characterize ganglionic receptor subtypes with specific subunit composition reveals species-specific pharmacologic properties.
2012,
Pubmed
,
Xenbase
Stroth,
PACAP controls adrenomedullary catecholamine secretion and expression of catecholamine biosynthetic enzymes at high splanchnic nerve firing rates characteristic of stress transduction in male mice.
2013,
Pubmed
Whiteaker,
Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist.
2007,
Pubmed
,
Xenbase
de Diego,
Altered exocytosis in chromaffin cells from mouse models of neurodegenerative diseases.
2018,
Pubmed
del Barrio,
Calcium signalling mediated through α7 and non-α7 nAChR stimulation is differentially regulated in bovine chromaffin cells to induce catecholamine release.
2011,
Pubmed
