Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

Weiner, I. David; Verlander, Jill W.

doi:10.1016/j.semnephrol.2019.04.008

Cited by 28 publications

(21 citation statements)

References 97 publications

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“…Certainly, bTRPV3 is not the only NH 4 + transporting channel and there is good reason to believe that in the rumen, in Xenopus oocytes, and in other parts of the gut, multiple types of non-selective cation channels should be considered when searching for pathways for the uptake of ammonium [58].…”

Section: Discussionmentioning

confidence: 99%

The TRPV3 channel of the bovine rumen: localization and functional characterization of a protein relevant for ruminal ammonia transport

Liebe

Kaessmeyer

et al. 2020

Pflugers Arch - Eur J Physiol

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Large quantities of ammonia (NH3 or NH4+) are absorbed from the gut, associated with encephalitis in hepatic disease, poor protein efficiency in livestock, and emissions of nitrogenous climate gasses. Identifying the transport mechanisms appears urgent. Recent functional and mRNA data suggest that absorption of ammonia from the forestomach of cattle may involve TRPV3 channels. The purpose of the present study was to sequence the bovine homologue of TRPV3 (bTRPV3), localize the protein in ruminal tissue, and confirm transport of NH4+. After sequencing, bTRPV3 was overexpressed in HEK-293 cells and Xenopus oocytes. An antibody was selected via epitope screening and used to detect the protein in immunoblots of overexpressing cells and bovine rumen, revealing a signal of the predicted ~ 90 kDa. In rumen only, an additional ~ 60 kDa band appeared, which may represent a previously described bTRPV3 splice variant of equal length. Immunohistochemistry revealed staining from the ruminal stratum basale to stratum granulosum. Measurements with pH-sensitive microelectrodes showed that NH4+ acidifies Xenopus oocytes, with overexpression of bTRPV3 enhancing permeability to NH4+. Single-channel measurements revealed that Xenopus oocytes endogenously expressed small cation channels in addition to fourfold-larger channels only observed after expression of bTRPV3. Both endogenous and bTRPV3 channels conducted NH4+, Na+, and K+. We conclude that bTRPV3 is expressed by the ruminal epithelium on the protein level. In conjunction with data from previous studies, a role in the transport of Na+, Ca2+, and NH4+ emerges. Consequences for calcium homeostasis, ruminal pH, and nitrogen efficiency in cattle are discussed.

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Section: Discussionmentioning

confidence: 99%

The TRPV3 channel of the bovine rumen: localization and functional characterization of a protein relevant for ruminal ammonia transport

Liebe

Kaessmeyer

et al. 2020

Pflugers Arch - Eur J Physiol

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“…Rh glycoproteins Rhbg and Rhcg are the primary proteins that mediate collecting duct ammonia secretion, and their expression generally parallels changes in ammonia excretion (10,16,52). However, KS-AR-KO did not alter significantly Rhbg protein expression in either male or female KS-AR-KO mice in either the cortex or inner stripe of the outer medulla (Fig.…”

Section: Effect Of Kidney-specific Ar Deletion On Ammonia Transportersmentioning

confidence: 91%

“…NKCC2 mediates TAL ammonia reabsorption (10,16,52). In male mice, KS-AR-KO increased NKCC2 protein expression using immunoblot analysis significantly; in female mice, there was no significant change (Fig.…”

Section: Effect Of Kidney-specific Ar Deletion On Ammonia Transportersmentioning

confidence: 92%

“…Renal ammonia excretion involves coordinated NH 3 / NH þ 4 transport by specific membrane proteins (10,16,52). This involves transporters in the proximal tubule (NHE3), TAL of the loop of Henle (NKCC2), and collecting duct In males, proximal tubules appeared sparser in KS-AR-KO kidneys compared with WT kidneys.…”

Section: Effect Of Kidney-specific Ar Deletion On Ammonia Transportersmentioning

confidence: 99%

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Role of the renal androgen receptor in sex differences in ammonia metabolism

Harris

Castro

Lee

et al. 2021

American Journal of Physiology-Renal Physiology

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Background: There are sex differences in renal ammonia metabolism and structure, many of which are mediated by testosterone. This study's goal was to determine the role of renal expression of testosterone's canonical receptor, androgen receptor (AR), in these sexual dimorphisms. Methods: We studied mice with kidney-specific AR deletion (KS-AR-KO) generated using Cre/loxP techniques; control mice were Cre-negative littermates (WT). Results: In male, but not female, mice, KS-AR-KO increased ammonia excretion, which eliminated sex differences. Although renal structural size typically parallel ammonia excretion, KS-AR-KO decreased kidney size, cortical proximal tubule volume density and cortical proximal tubule cell height in males; neither were altered in females and collecting duct volume density was unaltered in both sexes. Analysis of key protein involved in ammonia handling showed in male mice that KS-AR-KO increased both PEPCK and NKCC2 expression, and decreased NHE3 and NBCe1-A expression. In female mice, KS-AR-KO did not alter these parameters. These effects occurred even though KS-AR-KO did not alter plasma testosterone, food intake or serum Na+, K+, or HCO3- significantly in either sex. Conclusions: AR-dependent signaling pathways in male, but not female, kidney regulate PEPCK and NKCC2 expression and lead to the sexual differences in ammonia excretion. Opposing effects on NHE-3 and NBCe1-A expression likely limit the magnitude of ammonia excretion changes. Since AR is not present in the TAL, the effect of KS-AR-KO on NKCC2 expression is indirect. Finally, AR mediates the greater kidney size and PT volume density in male than in female mice.

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“…The study revealed changes in glutamine metabolism (i.e., higher plasma glutamine and γ-glutamyl-glutamine levels in fearful vs. non-fearful dogs). The essential AA glutamine serves not only as a precursor for the neurotransmitter glutamate, the most abundant and primary excitatory neurotransmitter in the central nervous system, but also for the neurotransmitter GABA [39], for antioxidant glutathione [40], protein, nucleotide and nucleic acid synthesis [41], as a substrate for gluconeogenesis [41] and ammonia genesis [42]. Glutamine actions in the brain are mostly mediated by the degradation of glutamine to glutamate as a part of the glutamate-glutamine cycle [39].…”

Section: Metabolomics In Anxiety Modelsmentioning

confidence: 99%

Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

2020

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Biomarkers are a recent research target within biological factors of psychiatric disorders. There is growing evidence for deriving biomarkers within psychiatric disorders in serum or urine samples in humans, however, few studies have investigated this differentiation in brain or cerebral fluid samples in psychiatric disorders. As brain samples from humans are only available at autopsy, animal models are commonly applied to determine the pathogenesis of psychiatric diseases and to test treatment strategies. The aim of this review is to summarize studies on biomarkers in animal models for psychiatric disorders. For depression, anxiety and addiction disorders studies, biomarkers in animal brains are available. Furthermore, several studies have investigated psychiatric medication, e.g., antipsychotics, antidepressants, or mood stabilizers, in animals. The most notable changes in biomarkers in depressed animal models were related to the glutamate-γ-aminobutyric acid-glutamine-cycle. In anxiety models, alterations in amino acid and energy metabolism (i.e., mitochondrial regulation) were observed. Addicted animals showed several biomarkers according to the induced drugs. In summary, animal models provide some direct insights into the cellular metabolites that are produced during psychiatric processes. In addition, the influence on biomarkers due to short- or long-term medication is a noticeable finding. Further studies should combine representative animal models and human studies on cerebral fluid to improve insight into mental disorders and advance the development of novel treatment strategies.

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Emerging Features of Ammonia Metabolism and Transport in Acid-Base Balance

Cited by 28 publications

References 97 publications

The TRPV3 channel of the bovine rumen: localization and functional characterization of a protein relevant for ruminal ammonia transport

The TRPV3 channel of the bovine rumen: localization and functional characterization of a protein relevant for ruminal ammonia transport

Role of the renal androgen receptor in sex differences in ammonia metabolism

Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

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