Multiple nicotinic acetylcholine receptor α-subunits are expressed in the arterial system of the rat

Brüggmann, Dörthe; Lips, Katrin Susanne; Pfeil, Uwe; Haberberger, Rainer Viktor; Kummer, Wolfgang

doi:10.1007/s00418-002-0475-2

Cited by 45 publications

(28 citation statements)

References 37 publications

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“…2). Vascular smooth muscle cells are known to express nicotinic acetylcholine receptors (Bruggmann et al, 2002, 2003); however, to our knowledge, this is the first demonstration of the localization of nicotinic acetylcholine receptors at podosomes and podosome rosettes and the first report of nicotinic acetylcholine receptor-mediated formation of podosome rosettes in vascular smooth muscle cells.…”

Section: Discussionmentioning

confidence: 81%

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Gu¹,

Fonseca²,

Hai³

2013

Vascular Pharmacology

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Cigarette smoking is a significant risk factor for atherosclerosis, which involves the invasion of vascular smooth muscle cells (VSMCs) from the media to intima. A hallmark of many invasive cells is actin cytoskeletal remodeling in the form of podosomes, accompanied by extracellular matrix (ECM) degradation. A7r5 VSMCs form podosomes in response to PKC activation. In this study, we found that cigarette smoke extract, nicotine, and the cholinergic agonist, carbachol, were similarly effective in inducing the formation of podosome rosettes in A7r5 VSMCs. α-Bungarotoxin and atropine experiments confirmed the involvement of nicotinic acetylcholine receptors (nAChRs). Western blotting and immunofluorescence experiments revealed the aggregation of nAChRs at podosome rosettes. Cycloheximide experiments and media exchange experiments suggested that autocrine factor(s) and intracellular phenotypic modulation are putative mechanisms. In situ zymography experiments indicated that, in response to PKC activation, nicotine-treated cells degraded ECM near podosome rosettes, and possibly endocytose ECM fragments to intracellular compartments. Invasion assay of human aortic smooth muscle cells indicated that nicotine and PKC activation individually and synergistically enhanced cell invasion through ECM. Results from this study suggest that nicotine enhances the ability of VSMCs to degrade and invade ECM. nAChR activation, actin cytoskeletal remodeling and phenotypic modulation are possible mechanisms.

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Section: Discussionmentioning

confidence: 81%

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Gu¹,

Fonseca²,

Hai³

2013

Vascular Pharmacology

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“…Although cigarette smoke is a complex mixture, nicotine is considered the main toxic and addictive compound of tobacco and a clinical risk factor for atherosclerosis (2–4). Nicotine activates a family of receptors involved in endogenous cholinergic signaling pathways (4). Two different types of nicotinic acetylcholine receptors are distinguished.…”

mentioning

confidence: 99%

“…The presence of neuronal nicotinic acetylcholine receptors (nAChRs) at locations unrelated to synaptic activity supports the hypothesis that acetylcholine may have cellular functions mediated by nicotinic receptors (5). nAChRs are present on nerve fibers innervating blood vessels, and there is growing evidence for an nAChR-mediated direct effect of nicotine on the arterial wall (4–6). The presence of nAChRs in a variety of non-neuronal cells, unrelated to synaptic activity, suggests that nicotine causes some of its toxic effects in the respiratory and cardiovascular systems by binding to nAChRs in these organs (5).…”

mentioning

confidence: 99%

“…Neuronal nAChRs have been shown to assemble as a homogeneous ( α 7-, α 9-, and α 10-receptors) or heterogeneous (e.g., α 4 β 2-receptor) pentamer of α - and β -subunits, including α 2– α 7 and β 2– β 4. α 7-, α 9-, and α 10-subunits are also able to assemble in functional α -heteropentamers (4,7–9). The composition of subunits determines ligand specificity, ligand affinity, cation permeability, and channel kinetics (10).…”

mentioning

confidence: 99%

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Feasibility of [18F]-2-Fluoro-A85380-PET Imaging of Human Vascular Nicotinic Acetylcholine Receptors In Vivo

Bucerius

Manka

Schmaljohann

et al. 2012

JACC: Cardiovascular Imaging

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OBJECTIVES The aim of this feasibility study was to evaluate [18F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders. BACKGROUND [18F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls. METHODS [18F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson’s disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [18F]-2-Fluoro-A85380 uptake in the arteries were also assessed. RESULTS [18F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [18F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together. CONCLUSIONS [18F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson’s disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature.

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“…Since after inhibiting the muscarinic receptors with 4-DAMP the remaining site of action of carbachol would be with nicotinic receptors, it is plausible to hypothesize that nicotinic receptors might modulate purinergic receptor desensitization. Recently, several nicotinic receptor subtypes have been described in vascular smooth muscle [6]. Although we have not provided any direct evidence of putative interaction between nicotinic and purinergic receptors in the bladder, other studies have shown that nicotinic and purinergic receptors can negatively interact with each other in the neural cells of sympathetic or enteric ganglia [2, 21, 33].…”

Section: Discussionmentioning

confidence: 56%

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

Lai

Muñoz

Smith

et al. 2011

Brain Research Bulletin

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The purpose of this study was to examine the pharmacologic plasticity of cholinergic, non-adrenergic non-cholinergic (NANC), and purinergic contractions in neurogenic bladder strips from spinal cord injured (SCI) rats. Bladder strips were harvested from female rats three to four weeks after T9–T10 spinal cord transection. The strips were electrically stimulated using two experimental protocols to compare the contribution of muscarinic and NANC/purinergic contractions in the presence and the absence of carbachol or muscarine. The endpoints of the study were: (1) percent NANC contraction that was unmasked by the muscarinic antagonist 4-DAMP, and (2) P2X purinergic contraction that was evoked by α,β–methylene ATP. NANC contraction accounted for 78.5% of the neurally evoked contraction in SCI bladders. When SCI bladder strips were treated with carbachol (10 µM) prior to 4-DAMP (500 nM), the percent NANC contraction decreased dramatically to only 13.1% of the neurally evoked contraction (p=0.041). This was accompanied by a substantial decrease in α,β–methylene ATP evoked P2X contraction, and desensitization of purinergic receptors (the ratio of subsequent over initial P2X contraction decreased from 97.2% to 42.1%, p=0.0017). Sequential activation of the cholinergic receptors with carbachol (or with muscarine in neurally intact bladders) and unmasking of the NANC response with 4-DAMP switched the neurally evoked bladder contraction from predominantly NANC to predominantly cholinergic. We conclude that activation of muscarinic receptors (with carbachol or muscarine) blocks NANC and purinergic contractions in neurally intact or in SCI rat bladders. The carbachol-induced inhibition of the NANC contraction is expressed more in SCI bladders compared to neurally intact bladders. Along with receptor plasticity, this change in bladder function may involve P2X-independent mechanisms.

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Multiple nicotinic acetylcholine receptor α-subunits are expressed in the arterial system of the rat

Cited by 45 publications

References 37 publications

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Nicotinic acetylcholine receptor mediates nicotine-induced actin cytoskeletal remodeling and extracellular matrix degradation by vascular smooth muscle cells

Feasibility of [18F]-2-Fluoro-A85380-PET Imaging of Human Vascular Nicotinic Acetylcholine Receptors In Vivo

Plasticity of non-adrenergic non-cholinergic bladder contractions in rats after chronic spinal cord injury

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