Request Demo

Last update 23 Jan 2025

NHE

Last update 23 Jan 2025

Basic Info

Synonyms

Na(+)/H(+) exchanger 10, NHE, NHE-10

+ [11]

Introduction

Sperm-specific sodium/hydrogen exchanger involved in intracellular pH regulation of spermatozoa. Required for sperm motility and fertility. Involved in sperm cell hyperactivation, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for the expression and bicarbonate regulation of the soluble adenylyl cyclase (sAC) (By similarity).

Drugs associated with NHE

KBR-9032

Target

NHE

Mechanism

NHE inhibitors

Active Org.-

Originator Org.

Organon KK

Active Indication-

Inactive Indication

Arrhythmias, Cardiac [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NHE

100 Translational Medicine associated with NHE

0 Patents (Medical) associated with NHE

1,307

Literatures (Medical) associated with NHE

01 Dec 2025·Journal of Sport and Health Science

Multiscale hamstring muscle adaptations following 9 weeks of eccentric training

Article

Author: Hodges, Paul W. ; Hodges, Paul W ; Delp, Scott L ; Lichtwark, Glen A ; Pincheira, Patricio A ; Delp, Scott L. ; S, Anoosha Pai ; Gurchiek, Reed D ; Andrews, Max H ; Pincheira, Patricio A. ; Lichtwark, Glen A. ; Chaudhari, Akshay S ; Chaudhari, Akshay S. ; Andrews, Max H. ; Gurchiek, Reed D.

BACKGROUNDEccentric training, such as Nordic hamstring exercise (NHE) training, is commonly used as a preventive measure for hamstring strains. Eccentric training is believed to induce lengthening of muscle fascicles and to be associated with the addition of sarcomeres in series within muscle fibers. However, the difficulty in measuring sarcomere adaptation in human muscles has severely limited information about the precise mechanisms of adaptation. This study addressed this limitation by measuring the multiscale hamstring muscle adaptations in response to 9 weeks of NHE training and 3 weeks of detraining.METHODSTwelve participants completed 9 weeks of supervised NHE training, followed by a 3-week detraining period. We assessed biceps femoris long-head (BFlh) muscle fascicle length, sarcomere length, and serial sarcomere number in the central and distal regions of the muscle. Additionally, we measured muscle volume and eccentric strength at baseline, post-training, and post-detraining.RESULTSNHE training over 9 weeks induced significant architectural and strength adaptations in the BFlh muscle. Fascicle length increased by 19% in the central muscle region and 33% in the distal muscle region. NHE also induced increases in serial sarcomere number (25% in the central region and 49% in the distal region). BFlh muscle volume increased by 8%, and knee flexion strength increased by 40% with training. Following 3 weeks of detraining, fascicle length decreased by 12% in the central region and 16% in the distal region along with reductions in serial sarcomere number.CONCLUSIONNine weeks of NHE training produced substantial, region-specific increases in BFlh muscle fascicle length, muscle volume, and force generation. The direct measurement of sarcomere lengths revealed that the increased fascicle length was accompanied by the addition of sarcomeres in series within the muscle fascicles.

14 Dec 2024·Cardiovascular Research

Zinc-alpha2-glycoprotein modulates blood pressure by regulating renal lipid metabolism reprogramming-mediated urinary Na+ excretion in hypertension

Article

Author: Chen, Caiyu ; Yang, Jian ; Zheng, Shuo ; Schini-Kerth, Valérie B ; Lei, Lifu ; Deng, Chunyan ; Zhou, Xiaoxin ; Wang, Xiaoliang ; Du, Chengfeng ; Chen, Lin

AbstractAimsOrgans modulating blood pressure are associated with a common cytokine known as adipokines. We chose Zinc-alpha2-glycoprotein (ZAG) due to its prioritized transcriptional level in the database. Previous studies showed that ZAG is involved in metabolic disorders. The aim of this study was to investigate its role in hypertension.Methods and resultsSerum ZAG levels were assessed in hypertensive and healthy participants. Blood pressure was monitored in Azgp1−/− mice and other animal models by 24-hour ambulatory implanted telemetric transmitters and tail-cuff method. Multi-omics analysis of proteomics and metabolomics were performed to explore possible mechanisms. Serum ZAG levels were significantly decreased and associated with morning urine Na+ excretion in hypertensive participants in a cross-sectional study. This study firstly reported that Azgp1−/− mice exhibited increased blood pressure and impaired urinary Na+ excretion, which were restored by AAV9-mediated renal tubule Azgp1 rescue. Azgp1 knockout caused the reprogramming of renal lipid metabolism, and increased Na+/H+-exchanger (NHE) activity in the renal cortex. Administration with a NHE inhibitor EIPA reversed the impaired urinary Na+ excretion in Azgp1−/− mice. Moreover, the activity of carnitine palmitoyltransferase 1 (CPT1), a key enzyme of fatty acid β-oxidation, was decreased, and the levels of malonyl-CoA, an inhibitor of CPT1, were increased in renal cortex of Azgp1−/− mice. Renal Cpt1 rescue improved urinary Na+ excretion and blood pressure in Azgp1−/− mice, accompanied by decreased renal fatty acid levels and NHE activity. Finally, administration of recombinant ZAG protein improved blood pressure and urinary Na+ excretion in spontaneous hypertension rats.ConclusionDeficiency of Azgp1 increased the malonyl CoA-mediated inhibition of CPT1 activity, leading to renal lipid metabolism reprogramming, resulting in accumulated fatty acids and increased NHE activity, subsequently decreasing urinary Na+ excretion and causing hypertension. These findings may provide a potential kidney-targeted therapy in the prevention and treatment of hypertension.

01 Dec 2024·Journal of Biological Chemistry

The sodium–proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm

Article

Author: Treviño, Claudia L. ; Luque, Guillermina M ; Buffone, Mariano G ; De la Vega Beltrán, José L ; Treviño, Claudia L ; Krapf, Dario ; Carruba, Micaela ; De la Vega Beltrán, José L. ; Buffone, Mariano G. ; Gentile, Iñaki ; Novero, Analia G ; Krapf, Diego ; Ritagliati, Carla ; Schiavi-Ehrenhaus, Liza J. ; Torres Rodríguez, Paulina ; Luque, Guillermina M. ; Nishigaki, Takuya ; Schiavi-Ehrenhaus, Liza J ; Rodríguez, Paulina Torres ; Stival, Cintia ; Santi, Celia M ; Novero, Analia G. ; Darszon, Alberto ; Santi, Celia M.

Sperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components, such as bicarbonate, albumin, Ca²⁺, and energy substrates, among others. Genetic and pharmacological studies have underscored the unique significance of the K⁺ channel SLO3 in membrane potential hyperpolarization, as evidenced by the infertility of mice lacking its expression. Notably, two key molecular events, sperm hyperpolarization and intracellular alkalinization, are central to the capacitation process. SLO3 is activated by alkalinization. However, the molecular mechanisms responsible for intracellular alkalization and activation of SLO3 are not completely understood. In this study, we examined the impact of Na⁺/H⁺ exchangers (NHEs) on mouse sperm membrane hyperpolarization during capacitation. Pharmacological inhibition of the NHE1 blocked membrane hyperpolarization. A similar effect was observed in sperm deficient of the Ca²⁺ channel CatSper because of NHE1 not being activated by Ca²⁺. In addition, the sperm-specific NHE (sNHE) KO did not show membrane hyperpolarization upon capacitation or induction with cAMP analogs. Our results show that sNHE is dually modulated by cAMP and membrane hyperpolarization probably through its cyclic nucleotide-binding domain and the voltage-sensor motif, respectively. Together, sNHE and NHE1 provide the alkalinization need for SLO3 activation during capacitation.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

NHE

Basic Info

Related

Analysis