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Scientific Reports Jul 2017Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH...
Genetically encoded pH-sensors are widely used in studying cell membrane trafficking and membrane protein turnover because they render exo-/endocytosis-associated pH changes to fluorescent signals. For imaging and analysis purposes, high concentration ammonium chloride is routinely used to alkalize intracellular membrane compartments under the assumption that it does not cause long-term effects on cellular processes being studied like neurotransmission. However, pathological studies about hyperammonemia have shown that ammonium is toxic to brain cells especially astrocytes and neurons. Here, we focus on ammonium's physiological impacts on neurons including membrane potential, cytosolic Ca and synaptic vesicles. We have found that extracellularly applied ammonium chloride as low as 5 mM causes intracellular Ca-increase and a reduction of vesicle release even after washout. The often-used 50 mM ammonium chloride causes more extensive and persistent changes, including membrane depolarization, prolonged elevation of intracellular Ca and diminution of releasable synaptic vesicles. Our findings not only help to bridge the discrepancies in previous studies about synaptic vesicle release using those pH-sensors or other vesicle specific reporters, but also suggest an intriguing relationship between intracellular pH and neurotransmission.
Topics: Ammonium Chloride; Animals; Calcium; Cell Membrane; Mice; Neurons; Rats, Sprague-Dawley; Synaptic Vesicles
PubMed: 28698583
DOI: 10.1038/s41598-017-05338-5 -
Nature Communications Oct 2023Ammonium (NH), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has...
Ammonium (NH), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NHCl). Extracellular NHCl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NHCl relative to acid stimuli. Taste responses to NHCl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1 mouse strain. Behavioral aversion of mice to NHCl, reduced in Skn-1a mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NHCl and a previously undescribed channel activation mechanism.
Topics: Animals; Humans; Mice; Ammonium Chloride; HEK293 Cells; Protons; Taste; Taste Buds
PubMed: 37798269
DOI: 10.1038/s41467-023-41637-4 -
International Journal of Molecular... May 2022It is known that ammonium has a higher permeability through anion exchange and bipolar membranes compared to K+ cation that has the same mobility in water. However, the...
It is known that ammonium has a higher permeability through anion exchange and bipolar membranes compared to K+ cation that has the same mobility in water. However, the mechanism of this high permeability is not clear enough. In this study, we develop a mathematical model based on the Nernst−Planck and Poisson’s equations for the diffusion of ammonium chloride through an anion-exchange membrane; proton-exchange reactions between ammonium, water and ammonia are taken into account. It is assumed that ammonium, chloride and OH− ions can only pass through membrane hydrophilic pores, while ammonia can also dissolve in membrane matrix fragments not containing water and diffuse through these fragments. It is found that due to the Donnan exclusion of H+ ions as coions, the pH in the membrane internal solution increases when approaching the membrane side facing distilled water. Consequently, there is a change in the principal nitrogen-atom carrier in the membrane: in the part close to the side facing the feed NH4Cl solution (pH < 8.8), it is the NH4+ cation, and in the part close to distilled water, NH3 molecules. The concentration of NH4+ reaches almost zero at a point close to the middle of the membrane cross-section, which approximately halves the effective thickness of the diffusion layer for the transport of this ion. When NH3 takes over the nitrogen transport, it only needs to pass through the other half of the membrane. Leaving the membrane, it captures an H+ ion from water, and the released OH− moves towards the membrane side facing the feed solution to meet the NH4+ ions. The comparison of the simulation with experiment shows a satisfactory agreement.
Topics: Ammonia; Ammonium Chloride; Ammonium Compounds; Anions; Chlorides; Nitrogen; Permeability; Water
PubMed: 35628589
DOI: 10.3390/ijms23105782 -
International Journal of Infectious... Jul 2021The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections.
DESIGN
In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients.
RESULTS
A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively.
CONCLUSION
The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.
Topics: Ammonium Chloride; COVID-19; Humans; Outpatients; Pandemics; SARS-CoV-2; Standard of Care; Treatment Outcome
PubMed: 33878462
DOI: 10.1016/j.ijid.2021.04.043 -
British Medical Journal Aug 1961
Topics: Acidosis; Ammonium Chloride; Humans
PubMed: 14447351
DOI: No ID Found -
Birth Defects Research Nov 2021To determine the potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) to induce reproductive toxicity in CD® rats...
AIM
To determine the potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) to induce reproductive toxicity in CD® rats in two independent 2-generation reproduction studies conducted according to Good Laboratory Practices and standardized testing guidelines.
MATERIALS AND METHODS
Male and female rats (parents and offspring) were allowed continual free access to diets containing concentrations of ADBAC (0, 300, 1,000, or 2,000 ppm) or DDAC (0, 300, 750, or 1,500 ppm), beginning with F generation adults at 10 weeks prior to breeding.
RESULTS
No clinical signs of toxicity were observed in parental rats or their offspring in either study. Dietary exposure of parental rats to ADBAC or DDAC at the highest concentrations produced transient decreases in body weight and/or body weight changes with no or minimal corresponding reduction in food consumption. Offspring (F and F ) in the highest concentration group in each study also exhibited reduced body weights, often with a corresponding reduction in weight change, beginning on postnatal day (PND) 14 through weaning on PND 28. This reduction in pup body weight corresponded to initiation of self-feeding.
CONCLUSIONS
Based on reduced body weights, the no observed adverse effect level (NOAEL) for adult and offspring systemic toxicity was 1,000 ppm for ADBAC and 750 ppm for DDAC (equivalent to approximate daily oral doses of 59 and 45 mg/kg/day, respectively). The reproductive and developmental NOAEL for F , F , and F generation male and female rats was 2,000 ppm for ADBAC and 1,500 ppm for DDAC (equivalent to approximate daily oral doses of 118 and 91 mg/kg/day, respectively).
Topics: Ammonium Chloride; Animals; Benzalkonium Compounds; Chlorides; Female; Male; No-Observed-Adverse-Effect Level; Rats; Reproduction
PubMed: 34549546
DOI: 10.1002/bdr2.1955 -
PloS One 2022Microalgae have garnered widespread attention as a sustainable source of pharmaceuticals and nutraceuticals. As for extracting lipids from microalgae, the combination of...
Microalgae have garnered widespread attention as a sustainable source of pharmaceuticals and nutraceuticals. As for extracting lipids from microalgae, the combination of microwave-assisted extraction (MAE) and ionic liquids (IL) is shown to be promising. However, such an undertaking usually requires a large consumption of expensive ILs. This study innovatively employs tetramethyl ammonium chloride ([TMAm][Cl]) as an additive in water medium to associate with microwave-assisted ionic liquid extraction (MAILE) in extracting lipids from Nannochloropsis oceanica (N. oceanica) microalgae. In extraction, knowledge of reaction kinetics is crucial since it provides the foundation for developing, controlling, and improving the processes of extraction. Herein, using MAILE, lipids are extracted from N. oceanica microalgae and transesterified to eicosapentaenoic acid (EPA). Mass transfer kinetics are, therefore, investigated using the first and second-order rate law and Patricelli's model. In the development of models, the influence of temperature (60-90°C) and reaction time (1-25 min) on EPA extraction is empirically evaluated. From the thermodynamic study, the positive values of ΔS (+0.10 kJ mol-1K-1) and ΔH (+32.50 kJ mol-1) and the negative value of ΔG (-1.68 to -4.75 kJ mol-1) confirm that this process is endothermic in nature, irreversible and spontaneous. MAILE proves to be a promising approach for the extraction of high-quality EPAs. Due to its low cost, rapid operation, and environmental friendliness, it is seen to be suitable for both pharmaceutical and nutraceutical applications.
Topics: Ammonium Chloride; Eicosapentaenoic Acid; Ionic Liquids; Kinetics; Microalgae; Microwaves; Stramenopiles; Thermodynamics
PubMed: 35511804
DOI: 10.1371/journal.pone.0267626 -
Journal of Dairy Science Dec 1988Forty-eight Holstein cows with two or more previous lactations and no history of parturient paresis were randomly assigned to one of four prepartum diets in a 2 x 2... (Comparative Study)
Comparative Study
Forty-eight Holstein cows with two or more previous lactations and no history of parturient paresis were randomly assigned to one of four prepartum diets in a 2 x 2 factorial design to determine the effect of dietary supplementation with ammonium salts and Ca intake on serum Ca concentrations at calving. Four diets provided either 53 g total dietary Ca/d or 105 g Ca/d and were either supplemented with ammonium salts [100 g/d each of NH4Cl and (NH4)2SO4] or unsupplemented. Anion-cation balance of the diets, calculated as milliequivalents (Na + K)--(Cl + S), was -75 meq/kg DM with ammonium salts and +189 meq/kg DM without ammonium salts. Experimental diets were fed from 21 d prior to expected parturition until calving. Calcium intake during the feeding period did not affect the incidence of parturient paresis or serum concentrations of ionized Ca at calving. The incidence of parturient paresis was 4% with and 17% without the ammonium salts. Cows fed diets containing ammonium salts had higher serum ionized and total Ca concentrations at parturition. Serum concentrations of Mg, P, Na, K, and Cl on the day of parturition were unaffected by dietary treatment.
Topics: Ammonium Chloride; Ammonium Sulfate; Animals; Calcium, Dietary; Cattle; Cattle Diseases; Diet; Female; Parturient Paresis; Pregnancy
PubMed: 3235732
DOI: 10.3168/jds.S0022-0302(88)79935-X -
Birth Defects Research Jul 2021The prenatal developmental toxicity potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) was evaluated in...
The prenatal developmental toxicity potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) was evaluated in regulatory-compliant studies. Pregnant female CD rats (25/group) and New Zealand White rabbits (16/group) were administered ADBAC (0, 10, 30, or 100 mg/kg/day and 0, 1, 3, or 9 mg/kg/day, respectively), or DDAC (0, 1, 10, or 20 mg/kg/day and 0, 1, 3, or 10 mg/kg/day, respectively), by oral gavage on gestation days (GD) 6-15 for rats and GD 6-18 for rabbits. At scheduled termination (GD 21 for rats; GD 29 for rabbits), maternal necropsies were conducted and live fetuses were weighed and examined for external, visceral, and skeletal malformations and variations. Clinical signs of maternal toxicity were observed in rats and rabbits dosed with ADBAC, resulting in no-observed-adverse-effect levels (NOAELs) of 10 and 3 mg/kg/day, respectively. Despite the treatment-related maternal toxicity of ADBAC, the NOAEL for prenatal developmental toxicity was 100 and 9 mg/kg/day for rats and rabbits, respectively, the highest doses evaluated. Repeated oral doses of DDAC resulted in maternal toxicity in both species at the top two doses, with 25% mortality noted in rabbits at 10 mg/kg/day. No teratogenic effects were observed at any dose for either species. However, increased incidence of dead fetuses per litter and decreased fetal body weights were observed in rabbits at the maternally lethal dose of 10 mg/kg/day. The NOAEL for maternal toxicity of DDAC was 1 mg/kg/day for both species and the NOAEL for prenatal developmental toxicity was 20 and 3 mg/kg/day, for rats and rabbits, respectively.
Topics: Ammonium Chloride; Animals; Benzalkonium Compounds; Chlorides; Female; Fetal Weight; No-Observed-Adverse-Effect Level; Pregnancy; Rabbits; Rats
PubMed: 33749149
DOI: 10.1002/bdr2.1889 -
Journal of Oleo Science Sep 2020A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (THQC) was synthesized, which consisted of one triazine spacer group and six long...
A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (THQC) was synthesized, which consisted of one triazine spacer group and six long flexible hydrophobic chains. The molecular structure and aggregation behavior of THQC was investigated by nuclear magnetic resonance (NMR), surface tension, electrical conductivity, dynamic light scattering (DLS), transmission electron microscope (TEM), etc. The results show that the jellyfish-shaped THQC has better surface activity and lower surface tension than traditional ionic and Gemini surfactants in aqueous solution. There are two inflection points in the curve of conductivity versus concentration of the THQC aqueous solution, which correspond to the critical aggregation concentration (CAC) and the critical micelle concentration (CMC) respectively. The existence of CAC indicates that there is a pre-aggregation process before THQC forms micelles. The results of DLS and TEM show that network pre-aggregation, spherical aggregation and dense spherical aggregation were observed in different concentration of THQC aqueous solution, and the electrostatic equilibrium of the system subtly depends on the concentration of the solution. In addition, intramolecular and intermolecular hydrogen bonding is also an important factor. This study provides a method for studying the aggregation behavior and morphology of oligomeric surfactants with rigid spacer groups.
Topics: Ammonium Chloride; Chemical Phenomena; Dynamic Light Scattering; Electric Conductivity; Hydrogen Bonding; Micelles; Molecular Structure; Quaternary Ammonium Compounds; Solutions; Surface Tension; Surface-Active Agents; Triazines; Water
PubMed: 32788513
DOI: 10.5650/jos.ess20016