Expression of aquaporins, vasopressin type 2 receptor, and Na+-K+-Cl–cotransporters in the rat endolymphatic sac

Nishimura, Masahiko; Kakigi, Akinobu; Takeda, Taizo; Takeda, Setsuko; Doi, Kunio

doi:10.1080/00016480802441754

Cited by 36 publications

(31 citation statements)

References 21 publications

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“…This is partially due to the fact that expression of NKCC2 has been only recently found in extratubular cells. Indeed, NKCC2 is expressed in specialised neurons of the gastrointestinal tract or interneurons (Gavrikov et al 2006, Xue et al 2009, Zhu et al 2011 and in cells of the gastric, intestinal, endolymphatic sac and olfactory epithelia (Akiyama et al 2007, Nickell et al 2007, Nishimura et al 2009, Xue et al 2009, Zhu et al 2011. In fact, low levels of Slc12a1 mRNAs appear to be widely distributed in human tissues (Di Fulvio & Alvarez-Leefmans 2009).…”

Section: Introductionmentioning

confidence: 99%

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Alshahrani

Fulvio

2012

Journal of Endocrinology

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The intracellular chloride concentration ([Cl co-transporters 2 and 1 respectively. We show that mice lacking functional alleles of the Slc12a2 gene exhibit better fasting glycaemia, increased insulin secretion in response to glucose, and improved glucose tolerance when compared with wildtype (WT). This phenomenon correlated with increased sensitivity of b-cells to glucose in vitro and with increased b-cell mass. Further, administration of low doses of BTD to mice deficient in Slc12a2 worsened their glucose tolerance, and low concentrations of BTD directly inhibited glucose-stimulated insulin secretion from b-cells deficient in Slc12a2 but expressing intact Slc12a1 genes. Together, our results suggest for the first time that the Slc12a2 gene is not necessary for insulin secretion and that its absence increases b-cell secretory capacity. Further, impairment of insulin secretion with BTD in vivo and in vitro in islets lacking Slc12a2 genes unmasks a potential new role for Slc12a1 in b-cell physiology.

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Section: Introductionmentioning

confidence: 99%

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Alshahrani

Fulvio

2012

Journal of Endocrinology

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“…8 Recently, it has come to light that this mechanism has a crucial role not only in the kidney but also in the inner ear. In addition, the following evidence has accumulated to suggest that VP is closely associated with the formation of EH: (1) plasma levels of arginine VP are higher in patients with MD and may depend on the phase that the patient is in, [9][10][11] (2) acute and chronic application of arginine VP produces EH in guinea-pigs and rats, [12][13][14] (3) V2 receptor mRNA is expressed in rat and human inner ear, [15][16][17][18] and (4) expression of V2 receptor mRNA in the rat inner ear is downregulated by VP application. 19 Such accumulated evidence has led to the assumption that production of endolymph is controlled by VP-AQP2 system.…”

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confidence: 99%

Morphological and functional changes in a new animal model of Ménière's disease

Egami

Kakigi

Sakamoto

et al. 2013

Laboratory Investigation

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The purpose of this study was to clarify the underlying mechanism of vertiginous attacks in Ménière's disease (MD) while obtaining insight into water homeostasis in the inner ear using a new animal model. We conducted both histopathological and functional assessment of the vestibular system in the guinea-pig. In the first experiment, all animals were maintained 1 or 4 weeks after electrocauterization of the endolymphatic sac of the left ear and were given either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal bones from both ears were harvested and the extent of endolymphatic hydrops was quantitatively assessed. In the second experiment, either 1 or 4 weeks after surgery, animals were assessed for balance disorders and nystagmus after the administration of saline or desmopressin. In the first experiment, the proportion of endolymphatic space in the cochlea and the saccule was significantly greater in ears that survived for 4 weeks after surgery and were given desmopressin compared with other groups. In the second experiment, all animals that underwent surgery and were given desmopressin showed spontaneous nystagmus and balance disorder, whereas all animals that had surgery but without desmopressin administration were asymptomatic. Our animal model induced severe endolymphatic hydrops in the cochlea and the saccule, and showed episodes of balance disorder along with spontaneous nystagmus. These findings suggest that administration of desmopressin can exacerbate endolymphatic hydrops because of acute V2 (vasopressin type 2 receptor)-mediated effects, and, when combined with endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that are similar to the vertiginous attacks in patients with MD. Ménière's disease (MD) is a well-known inner ear disorder characterized by symptoms including recurring attacks of vertigo typically lasting for hours, fluctuating sensorineural hearing loss, and tinnitus. Since the milestone findings on the temporal bones of MD patients, 1,2 endolymphatic hydrops (EH) has been considered as the histopathological origin of MD, as characteristic morphological changes were reported to be produced by surgical obstruction of the endolymphatic sac (ES) in guinea-pig. 3 This observation indicates that malabsorption of endolymph in the ES is one of the possible mechanisms underlying the development of EH. This experimentally induced EH has been frequently used as an animal model to investigate the pathogenesis of inner ear disorders associated with EH. In terms of vestibular function, while canal dysfunction and/or spontaneous nystagmus have been occasionally observed in this animal model, 4,5 episodes of vertiginous attack or balance disorder have only rarely been observed. 6 In other words, this model is insufficient for fully representing the common symptoms of MD.Water homeostasis of the inner ear is essential for maintaining the functions of hearing and balance. EH is considered to be the result of disruption of inner ear water homeostasis, which ...

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“…NKCC-2 was originally known as a kidney-specific cotransporter expressed only on the apical membrane of the TAL (Knepper and Brooks 2001;Mutig et al 2007). Its expression has been reported recently in human and rat ES (Nishimura et al 2008;Kakigi et al 2009); however, its detailed localization has not been reported. The present immunostaining results with specific anti-NKCC-2 antibody indicate that NKCC-2 is localized in the apical membranes of ES epithelia, specifically in the same pattern as in mammalian renal TAL (Knepper and Brooks 2001).…”

Section: Discussionmentioning

confidence: 97%

“…NKCC-2 is typically recognized as a kidney-specific ion transporter and is expressed in the apical membrane of the thick ascending limb (TAL) loop of Henle, where it is responsible for the reabsorption of ?20% of filtered NaCl (Gamba et al 1994). Recently, the protein expression of NKCC-2 in human and rat ES has been reported by using IHC (Nishimura et al 2008;Kakigi et al 2009); however, detailed tissue or cellular localization has not been reported. This study has elucidated the NKCC-2 localization pattern in each part of the ES and the coexpression pattern with Na 1 /K 1 -ATPase by immunohistochemical assessment, which may provide beneficial information to understand the ES ion transport system.…”

Section: /2clmentioning

confidence: 99%

The Detailed Localization Pattern of Na⁺/K⁺/2Cl⁻ Cotransporter Type 2 and Its Related Ion Transport System in the Rat Endolymphatic Sac

Akiyama

Miyashita

Matsubara

et al. 2010

J Histochem Cytochem.

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The endolymphatic sac (ES) is a part of the membranous labyrinth. ES is believed to perform endolymph absorption, which is dependent on several ion transporters, including Na+/K+/2Cl− cotransporter type 2 (NKCC-2) and Na+/K+-ATPase. NKCC-2 is typically recognized as a kidney-specific ion transporter expressed in the apical membrane of the absorptive epithelium. NKCC-2 expression has been confirmed only in the rat and human ES other than the kidney, but the detailed localization features of NKCC-2 have not been investigated in the ES. Thus, we evaluated the specific site expressing NKCC-2 by immunohistochemical assessment. NKCC-2 expression was most frequently seen in the intermediate portion of the ES, where NKCC-2 is believed to play an important role in endolymph absorption. In addition, NKCC-2 expression was also observed on the apical membranes of ES epithelial cells, and Na+/K+-ATPase coexpression was observed on the basolateral membranes of ES epithelial cells. These results suggest that NKCC-2 performs an important role in endolymph absorption and that NKCC-2 in apical membranes and Na+/K+-ATPase in basolateral membranes work coordinately in the ES in a manner similar to that in renal tubules.

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Expression of aquaporins, vasopressin type 2 receptor, and Na⁺-K⁺-Cl^–cotransporters in the rat endolymphatic sac

Abstract: mRNAs and proteins of AQP1-4, AQP6-9, V(2)-R, NKCC1, and NKCC2 were expressed, but AQP5 was not expressed in the rat endolymphatic sac.

Cited by 36 publications

References 21 publications

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Morphological and functional changes in a new animal model of Ménière's disease

The Detailed Localization Pattern of Na⁺/K⁺/2Cl⁻ Cotransporter Type 2 and Its Related Ion Transport System in the Rat Endolymphatic Sac

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Expression of aquaporins, vasopressin type 2 receptor, and Na+-K+-Cl–cotransporters in the rat endolymphatic sac

Abstract: mRNAs and proteins of AQP1-4, AQP6-9, V(2)-R, NKCC1, and NKCC2 were expressed, but AQP5 was not expressed in the rat endolymphatic sac.

Cited by 36 publications

References 21 publications

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Enhanced insulin secretion and improved glucose tolerance in mice with homozygous inactivation of the Na+K+2Cl− co-transporter 1

Morphological and functional changes in a new animal model of Ménière's disease

The Detailed Localization Pattern of Na+/K+/2Cl− Cotransporter Type 2 and Its Related Ion Transport System in the Rat Endolymphatic Sac

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About

Expression of aquaporins, vasopressin type 2 receptor, and Na⁺-K⁺-Cl^–cotransporters in the rat endolymphatic sac

The Detailed Localization Pattern of Na⁺/K⁺/2Cl⁻ Cotransporter Type 2 and Its Related Ion Transport System in the Rat Endolymphatic Sac