Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium

Zarghooni, Shirin; Wunsch, Julia; Bodenbenner, Martin; Brüggmann, Dörthe; Grando, Sergei A.; Schwantes, Ulrich; Wess, Jürgen; Kummer, Wolfgang; Lips, Katrin Susanne

doi:10.1016/j.lfs.2007.01.046

Cited by 87 publications

(75 citation statements)

References 29 publications

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“…nAChR function has also been reported in bronchial epithelia, where nAChRs expressed on the apical membrane (Maus et al, 1998) respond to non-neuronal autocrine/paracrine ACh release to regulate chloride permeability through the cystic fibrosis transmembrane conductance regulator (CFTR) channel (Maouche et al, 2013). Nonneural roles for nAChRs have also been identified in vascular endothelia (reviewed in Egleton et al, 2009), in urothelia (Zarghooni et al, 2007) and in keratinocytes (Grando et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

Feingold

Starc

O’Donnell

et al. 2016

Journal of Experimental Biology

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Pentameric ligand-gated ion channels ( pLGICs) constitute a large protein superfamily in metazoa whose role as neurotransmitter receptors mediating rapid, ionotropic synaptic transmission has been extensively studied. Although the vast majority of pLGICs appear to be neurotransmitter receptors, the identification of pLGICs in non-neuronal tissues and homologous pLGIC-like proteins in prokaryotes points to biological functions, possibly ancestral, that are independent of neuronal signalling. Here, we report the molecular and physiological characterization of a highly divergent, orphan pLGIC subunit encoded by the pHCl-2 (CG11340) gene, in Drosophila melanogaster. We show that pHCl-2 forms a channel that is insensitive to a wide array of neurotransmitters, but is instead gated by changes in extracellular pH. pHCl-2 is expressed in the Malpighian tubules, which are non-innervated renal-type secretory tissues. We demonstrate that pHCl-2 is localized to the apical membrane of the epithelial principal cells of the tubules and that loss of pHCl-2 reduces urine production during diuresis. Our data implicate pHCl-2 as an important source of chloride conductance required for proper urine production, highlighting a novel role for pLGICs in epithelial tissues regulating fluid secretion and osmotic homeostasis.

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Section: Discussionmentioning

confidence: 99%

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

Feingold

Starc

O’Donnell

et al. 2016

Journal of Experimental Biology

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“…In the mouse bladder, immunostaining for TRPV4 was strong in the basal and intermediate cell layers and weak or absent in the umbrella cell layer (28). In mouse and human bladder, M1 muscarinic ACh receptors (mAChRs) were predominantly expressed in the basal cells, M2 mAChRs were restricted to the umbrella cells, and M3, M4, and M5 mAChRs were expressed throughout the urothelium (15,59).…”

Section: Discussionmentioning

confidence: 99%

Functional TRP and ASIC-like channels in cultured urothelial cells from the rat

Kullmann

Shah²,

Birder³

et al. 2009

American Journal of Physiology-Renal Physiology

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Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca 2ϩ imaging techniques. The TRPV4 agonist 4␣-phorbol-12,13 didecanoate (4␣-PDD; 1-5 M) and the TRPA1/TRPM8 agonist icilin (50 -100 M) elicited transient currents in a high percentage of cells (Ͼ70%). 4␣-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 M). The TRPV1 agonist capsaicin (1-100 M) and the TRPA1/TRPM8 agonist menthol (5-200 M) elicited transient currents in a moderate percentage of cells (ϳ25%). All of these agonists increased intracellular calcium concentration ([Ca 2ϩ ]i). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4␣-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 M), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca 2ϩ ]i (pH 6.5) in ϳ50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 M). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca 2ϩ influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli. bladder; fura 2 calcium imaging; patch clamp TRANSIENT RECEPTOR POTENTIAL (TRP) channels are nonselective cation channels that function as sensors for various stimuli, including temperature, mechanical stretch, or chemicals (2, 53). They are highly expressed in primary sensory neurons, where they play a critical role in nociception, mechano-, and thermosensation. In these neurons, distinct sets of TRP channels are coexpressed in different populations of cells. This differential pattern of expression confers functional heterogeneity to primary sensory neurons, and it is the basis for detection of sensory information (8,16,31,32,53). TRPV1 is a capsaicin/heat/pH-sensitive channel (16,17); TRPV4 is an osmotic/temperature/mechanical and shear stress detector (24, 36); TRPM8 is a cold (Ͻ22-26°C)/menthol/icilin-activated channel (38, 41); and TRPA1 is a noxious cold-sensitive channel (Ͻ17°C), also sensitive to cinnamaldehyde, mustard oil, menthol, and icilin (4, 49).Immunohistochemistry and RT-PCR identified several TRP channels including TRPV1, TRPV4, TRPM8, and TRPA1 in the urothelium, a specialized epithelial tissue believed to be involved in the detection of chemical and mechanical information and the generation of sensory input from the bladder to the spinal cord (2, 3, 12, 13, 22-24, 28, 39, 48, 50). Since the di...

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“…Western blotting also confirmed urothelial expression of the ␣3-and ␣7-subunits. In the mouse urothelium, Zarghooni et al (306), also using RT-PCR, detected mRNAs coding for the nicotinic receptor subunits ␣2, ␣4, ␣5, ␣6, ␣7, ␣9, and 10, whereas the ␣3-subunit was not expressed. By immunohistochemistry, they localized subunit ␣9 exclusively in the umbrella cells, whereas the subunits ␣4, ␣7, and ␣10 were also detected in the intermediate and basal cell layers.…”

Section: Cholinergic Receptorsmentioning

confidence: 99%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

390

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium

Cited by 87 publications

References 29 publications

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

The orphan pentameric ligand-gated ion channelpHCl-2is gated by pH and regulates fluid secretion inDrosophilaMalpighian tubules

Functional TRP and ASIC-like channels in cultured urothelial cells from the rat

Urothelial Signaling

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