Characteristics of mammalian Rh glycoproteins (SLC42 transporters) and their role in acid–base transport

Nakhoul, Nazih L.; Hamm, L. Lee

doi:10.1016/j.mam.2012.05.013

Cited by 35 publications

(26 citation statements)

References 67 publications

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“…Expression of Rhag-like mRNA was found in the erythrocytes and spleen, while Rhcg-like mRNA expression was detected in the gill. This tissue distribution pattern supports the classification of Rh mRNAs (83,85,128). In situ hybridization using adjacent sections demonstrated that the mRNAs of GS, OTC, and Rhp2 were colocalized in the same nephron segment of the proximal tubule (Fig.…”

Section: Urea Synthesis In the Kidneysupporting

confidence: 82%

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Hyodo

Kakumura

Takagi

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption. Am J Physiol Regul Integr Comp Physiol 307: R1381-R1395, 2014. First published October 22, 2014 doi:10.1152/ajpregu.00033.2014.-For adaptation to highsalinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes. cartilaginous fish; kidney; osmoregulation; transporters; urea BODY FLUID REGULATION is essential for all organisms to survive in their respective habitats, including freshwater (FW), seawater (SW), and terrestrial environments. It is well known that teleost fish regulate their plasma Na ϩ and Cl Ϫ concentrations and osmolality at levels about one-third of SW. Meanwhile, cartilaginous fishes (sharks, skates, rays, and chimaeras) have adopted a unique osmoregulatory strategy for adaptation to the high-salinity marine environment. Cartilaginous fishes control plasma ions to levels approximately one-half of surrounding SW while they store high concentrations of the nitrogenous compound urea as an osmolyte (the so-called "ureosmotic strategy"). As a result, their body fluids are slightly hyperosmotic to surrounding SW (for instance, plasma osmolality of houndshark is 1,000 mosmol/kg H 2 O in SW of 988 mosmol/kg H 2 O; Ref. 53), and thus cartilaginous fishes do not typically suffer dehydration even in the high-osmolality SW environment. To maintain high concentration of urea in the body, urea production by the ornithine urea cycle (OUC) is essential. Investigations on the OUC enzymes have proved that the liver is the primary organ f...

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Section: Urea Synthesis In the Kidneysupporting

confidence: 82%

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Hyodo

Kakumura

Takagi

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…These observations suggest that increased Rhbg expression is not likely to be contributing to the decrease in ammonia excretion. Rhbg has also been suggested to function as a CO 2 transporter (16,42), but because intercalated cell CO 2 transport is necessary for intracellular H ϩ generation used for urinary acidification, and dietary protein restriction causes urine alkalinization, this function is unlikely to underlie its increased expression during dietary protein restriction. Importantly, collecting duct Rhbg expression does not appear to be necessary for the changes in renal ammonia excretion in response to dietary protein restriction.…”

Section: Discussionmentioning

confidence: 99%

Effect of dietary protein restriction on renal ammonia metabolism

Lee

Osis

Handlogten

et al. 2015

American Journal of Physiology-Renal Physiology

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Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction.

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“…These were only identified as NH 3 /NH 4 1 transporters in recent years (75,76). These proteins function as NH 3 /NH 4 1 transporters, clearly facilitating diffusion of NH 3 but also, probably including (at least for RhBG) electrogenic transport of NH 4 1 (77,78). RhBG is present in the basolateral membrane of type A ICs and can transport NH 4 1 and NH 3 into the cell, whereas RhCG, present at the apical membrane of several cell types (and in some circumstances, basolateral membrane), transports NH 3 into the lumen.…”

Section: Nhmentioning

confidence: 99%

Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

327

262

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Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

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Characteristics of mammalian Rh glycoproteins (SLC42 transporters) and their role in acid–base transport

Cited by 35 publications

References 67 publications

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Effect of dietary protein restriction on renal ammonia metabolism

Acid-Base Homeostasis

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