Expression of the High-Affinity Choline Transporter, CHT1, in the Neuronal and Non-neuronal Cholinergic System of Human and Rat Skin

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

doi:10.1046/j.1523-1747.2002.00182.x

Cited by 42 publications

(26 citation statements)

References 37 publications

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“…Recently, CHT1 immunoreactivity has been identified in human keratinocytes and HaCaT cells (9) and in ciliated cells of the tracheal epithelium (7) by immunohistochemistry. These authors suggested that CHT1 is a novel component of the intrinsic non-neuronal cholinergic system of the skin.…”

Section: Up [mentioning

confidence: 99%

“…CHT1 is a Cl − -and Na that is highly sensitive to the choline analogue HC-3, and it is thought to be part of the rate-limiting step in ACh synthesis. CHT1 is also expressed by subpopulations of non-neuronal cholinergic cells such as ciliated cells of the airway epithelium (7,8) and keratinocytes (9). However, functional studies have shown that the airway epithelial cell line A549 expresses both a Na + -dependent CHT1 and a lower-affinity Na + -independent choline transporter (10).…”

Section: Introductionmentioning

confidence: 99%

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Expression and Functional Characterization of Choline Transporter in Human Keratinocytes

et al. 2009

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Abstract. Choline is essential for synthesis of the major membrane phospholipid phosphatidylcholine. Moreover, it serves as a precursor for synthesis of the neurotransmitter acetylcholine (ACh). Keratinocytes of the epidermis synthesize and release ACh. The uptake of choline is the rate-limiting step in both ACh synthesis and choline phospholipid metabolism, and it is a prerequisite for keratinocyte proliferation. However, the nature of the choline transport system in keratinocytes is poorly understood. In this study, we examined the molecular and functional characterization of choline uptake into cultured human keratinocytes. Choline uptake into keratinocytes was independent of extracellular Na + , saturable, and mediated by a single transport system with an apparent Michaelis-Menten constant of 12.3 μM. Choline uptake was reduced when the keratinocyte membrane potential was depolarized by high K + . These results provide evidence that the choline transport activity is potential-sensitive. Various organic cations inhibit the choline transport system. RT-PCR demonstrated that keratinocytes expressed mRNA for choline transporter-like protein 1 (CTL1), mainly the CTL1a subtype. The present biochemical and pharmacological data suggest that CTL1a is functionally expressed in human keratinocytes and is responsible for the uptake of choline and organic cations in these cells.

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Section: Up [mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression and Functional Characterization of Choline Transporter in Human Keratinocytes

et al. 2009

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“…9). DISCUSSION Recently, the importance of small autacoids, primarily thought to be neurotransmitters, in mediating a variety of biological activities in the skin (9,(43)(44)(45) has been demonstrated. In particular, several studies have indicated that adenosine, via stimulation of its receptors, is involved in cell proliferation and cell death.…”

Section: Cl-ib-meca Inhibits Cell Proliferation and Erk1/2 Activation-inmentioning

confidence: 99%

A3 Adenosine Receptor Activation Inhibits Cell Proliferation via Phosphatidylinositol 3-Kinase/Akt-dependent Inhibition of the Extracellular Signal-regulated Kinase 1/2 Phosphorylation in A375 Human Melanoma Cells

Merighi

Benini

Mirandola

et al. 2005

Journal of Biological Chemistry

112

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“…CHT1 is also expressed in rat and human endothelial and smooth muscle cells (Lips et al, 2003). The mRNAs of choline acetyltransferase (the enzyme responsible for acetylcholine synthesis) and VAChT (the transporter responsible for loading acetylcholine into secretory vesicles and making acetylcholine available for release) are expressed in rat pulmonary arteries and in endothelial cells (ECs) isolated from human or porcine pulmonary blood vessels (Haberberger et al, 2002). Choline acetyltransferase protein is present and functional in primary cultures of human umbilical vein ECs (Kirkpatrick et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries

Zhang

Leung

Vanhoutte

2015

J Pharmacol Exp Ther

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Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F 2a and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endotheliumdependent, Nv-nitro-L-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl) acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae. By contrast, in SHR aortae, TRPV4 channels are opened, resulting in endothelial production of acetylcholine, which, in an autocrine manner, activates muscarinic receptors on neighboring cells to elicit endothelium-dependent relaxations in response to mild hypothermia.

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Expression of the High-Affinity Choline Transporter, CHT1, in the Neuronal and Non-neuronal Cholinergic System of Human and Rat Skin

Cited by 42 publications

References 37 publications

Expression and Functional Characterization of Choline Transporter in Human Keratinocytes

Expression and Functional Characterization of Choline Transporter in Human Keratinocytes

A3 Adenosine Receptor Activation Inhibits Cell Proliferation via Phosphatidylinositol 3-Kinase/Akt-dependent Inhibition of the Extracellular Signal-regulated Kinase 1/2 Phosphorylation in A375 Human Melanoma Cells

Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries

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