NHE-1 isoform of the Na+H+ antiport is expressed in the rat and rabbit esophagus

Shallat, Shelly; Schmidt, Larry; Reaka, Andrea; Rao, Donald D.; Chang, Eugene B.; Rao, Mrinalini C.; Ramaswamy, Krishnamurthy; Layden, Thomas J.

doi:10.1016/0016-5085(95)90626-6

Cited by 25 publications

(20 citation statements)

References 15 publications

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“…ZP had no effect on baseline pH int and blood flow, whereas ZP inhibited and delayed the CO 2 -induced hyperaemic response with no change in pH int (Supplementary fig 3C,D). In contrast, S3226, a selective NHE3 inhibitor, used as a negative control, since the oesophagus does not express NHE3, 23 had no effect on CO 2 -induced hyperaemia and pH int . Thus, the effect of selective NHE1 inhibition was distinct from that of AML, suggesting that AML at a concentration that confers selectivity for ion channels was inhibiting ASIC rather than NHE1.…”

Section: Resultsmentioning

confidence: 97%

“…Since AML may inhibit NHE1 activity expressed in oesophageal mucosa, 23 we examined the effect of the selective NHE1 inhibitor zoniporide (ZP, 0.1 mM) or the selective NHE3 inhibitor S3226 (10 µM) on pH int and blood flow. ZP or S3226 was perfused from t = 0 to t = 10 min (pretreatment), followed by the perfusion of high CO 2 solution for 10 min.…”

Section: Methodsmentioning

confidence: 99%

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CO2 chemosensing in rat oesophagus

Akiba

Mizumori

Kuo

et al. 2008

Gut

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Background Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO2, a permeant gas, rather than H+, permeates through the epithelium, and is converted to H+, producing an afferent neural signal by activating chemosensors. Methods The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO2 (PCO2 = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pHint) was measured with 5′,6′-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler. Results Perfusion of a high CO2 solution induced hyperaemia without changing pHint, mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO2-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa. Conclusions The response to CO2 perfusion suggests that CO2 diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO2 by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO2 permeation may explain how luminal H+ equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.

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Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

CO2 chemosensing in rat oesophagus

Akiba

Mizumori

Kuo

et al. 2008

Gut

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“…NHE1 is the only NHE isoform described and studied in the esophagus (274) and due to its prominent role in pH i regulation. Intracellular acidification activates NHE1 via a proton-sensing domain located within the fifth intracellular loop and the 11th transmembrane domain (299), a phenomenon further modified by regulatory elements located in the C-terminal tail.…”

Section: Na+/h+ Exchange In Esophageal Physiologymentioning

confidence: 99%

SLC9 Gene Family: Function, Expression, and Regulation

Kiela

2018

Comprehensive Physiology

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The Slc9 family of Na /H exchangers (NHEs) plays a critical role in electroneutral exchange of Na and H in the mammalian intestine as well as other absorptive and secretory epithelia of digestive organs. These transport proteins contribute to the transepithelial Na and water absorption, intracellular pH and cellular volume regulation as well as the electrolyte, acid-base, and fluid volume homeostasis at the systemic level. They also influence the function of other membrane transport mechanisms, affect cellular proliferation and apoptosis as well as cell migration, adherence to the extracellular matrix, and tissue repair. Additionally, they modulate the extracellular milieu to facilitate other nutrient absorption and to regulate the intestinal microbial microenvironment. Na /H exchange is inhibited in selected gastrointestinal diseases, either by intrinsic factors (e.g., bile acids, inflammatory mediators) or infectious agents and associated bacterial toxins. Disrupted NHE activity may contribute not only to local and systemic electrolyte imbalance but also to the disease severity via multiple mechanisms. In this review, we describe the cation proton antiporter superfamily of Na /H exchangers with a particular emphasis on the eight SLC9A isoforms found in the digestive tract, followed by a more integrative description in their roles in each of the digestive organs. We discuss regulatory mechanisms that determine the function of Na /H exchangers as pertinent to the digestive tract, their regulation in pathological states of the digestive organs, and reciprocally, the contribution of dysregulated Na /H exchange to the disease pathogenesis and progression. © 2018 American Physiological Society. Compr Physiol 8:555-583, 2018.

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“…On exposure to acid, esophageal epithelial cells regulate their pH primarily via the combined actions of Na + /H + antiport and Na + -dependent Cl - /HCO 3 - exchange 20 . NHE1 is the sole plasmalemmal Na + /H + exchanger isoform expressed in the rabbit and rat esophagus, 21 and is regulated allosterically (activated) by reduced pH i in a protein kinase C (PKC)-dependent mechanism 22 . In addition, epidermal growth factor (EGF), abundant in the saliva, exerts a cytoprotective effect in acid-exposed cells via Ca 2+ /calmodulin- and PKC-dependent activation of NHE1 23 .…”

Section: Na+/h+ Exchange In Esophageal and Gastric Pathologymentioning

confidence: 99%

Pathophysiology of Intestinal Na+/H+ Exchange

Gurney

Laubitz

Ghishan

et al. 2017

Cellular and Molecular Gastroenterology and Hepatology

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Several members of the SLC9A family of Na+/H+ exchangers are expressed in the gut, with varying expression patterns and cellular localization. Not only do they participate in the regulation of basic epithelial cell functions, including control of transepithelial Na+ absorption, intracellular pH (pHi), cell volume, and nutrient absorption, but also in cellular proliferation, migration, and apoptosis. Additionally, they modulate the extracellular milieu in order to facilitate other nutrient absorption and to regulate the intestinal microbial microenvironment. Na+/H+ exchangers are frequent targets of inhibition in gastrointestinal pathologies, either by intrinsic factors (e.g. bile acids, inflammatory mediators) or infectious agents and associated microbial toxins. Based on emerging evidence, disruption of NHE activity via impaired expression or function of respective isoforms may contribute not only to local and systemic electrolyte imbalance, but also to the disease severity via multiple mechanisms. Here, we review the current state of knowledge about the roles Na+/H+ exchangers play in the pathogenesis of disorders of diverse origin and affecting a range of GI tissues.

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NHE-1 isoform of the Na+H+ antiport is expressed in the rat and rabbit esophagus

Cited by 25 publications

References 15 publications

CO2 chemosensing in rat oesophagus

CO2 chemosensing in rat oesophagus

SLC9 Gene Family: Function, Expression, and Regulation

Pathophysiology of Intestinal Na+/H+ Exchange

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