Role of tubular secretion and carbonic anhydrase in vertebrate renal sulfate excretion

Abstract

/HCO 3 Ϫ exchange at the brushborder membrane, tubular carbonic anhydrase (CA) activity, CAII protein, and a proportion of tubular SO 4 2Ϫ secretion that is CA dependent. CA activity is required for about one-half of this net SO 4 2Ϫ secretion but is also required for about one-half of the net reabsorption in bird proximal epithelium. A CA-SO 4 2Ϫ /anion exchanger metabolon arrangement is proposed that may speed both the secretory and reabsorptive processes. renal proximal tubule; transport metabolon INORGANIC SO 4 2Ϫ IS THE SECOND most abundant anion in the sea and one of the most abundant anions in vertebrate plasma, with concentrations varying among species from 0.3 to 1.8 mM. This large tetrahedral divalent anion can be obtained from the diet (83) or oxidation of the sulfur-containing amino acids cysteine and methionine (77). Sulfoconjugation reactions are the initial detoxification process for many endogenous (e.g., steroid hormones) and xenobiotic compounds and are required for the activation of numerous biological molecules (e.g., heparin, cholecystokinin, and gastrin) (59). SO 4 2Ϫ is a major component of glycosaminoglycans (dermatan sulfate, chondroitin sulfate, keratan sulfate, and heparan sulfate), which are structural components of numerous tissues, including cartilage, bone, myelin, and basal lamina (40 ]) in the renal tubule lumen reduces Ca 2ϩ and Mg 2ϩ reabsorption (66). RENAL SULFATE CLEARANCEThe kidneys are the major avenue for SO 4 2Ϫ excretion in vertebrates. Nearly all of plasma SO 4 2Ϫ is ultrafilterable in mammals (4), whereas 80% and 47% of plasma SO 4 2Ϫ are ultrafilterable in birds (71) and fish (75), respectively. Variation in the estimates of the ultrafilterable fraction of plasma SO 4 2Ϫ in vertebrates may arise from species differences or variations in method of determination. Urine content is determined by glomerular filtration, tubular reabsorption, and tubular secretion. This review will focus on the latter and will provide only a brief overview of tubular reabsorption because it has been described in detail elsewhere (2,51,52,57).Reabsorption of filtered SO 4 2Ϫ occurs primarily in the proximal tubule (35) secretion does not occur in these animals. SO 4 2Ϫ loading apparently has no effect on the saturable reabsorptive transport maximum for SO 4 2Ϫ (Tm SO 4 2Ϫ ) in the renal tubule of the human, dog, and frog (3,28,48). In contrast, Tm SO 4 2Ϫ in rats is reduced ϳ50% after plasma SO 4 2Ϫ loading, indicating that adaptive mechanisms are in place to depress reabsorption, thus increasing excretion (27). Similarly, in domestic fowl, Tm SO 4 2Ϫ decreases with plasma SO 4 2Ϫ loading, leading to the conclusion that a fraction of the excreted SO 4 2Ϫ is the result of tubular secretion (30). Thiosulfate, an inhibitor of SO 4 2Ϫ transporters,

Molecular physiology and functional morphology of SO42– excretion by the kidney of seawater-adapted eels

“…The urine of marine teleosts is isotonic to their plasma but contains concentrations of SO 4 2-, Mg 2+ and Ca 2+ that are higher than those of SW. Renal SO 4 2-excretion is essential for SO 4 2-homeostasis in marine teleosts (Renfro, 1999), as shown in the flounder (Beyenbach et al, 1986;Dickman and Renfro, 1986;Pelis and Renfro, 2004;Renfro et al, 1999;Renfro and Pritchard, 1982;Renfro and Pritchard, 1983), goosefish (Berglund and Forster, 1958) and killifish (Cliff and Beyenbach, 1992).…”

Carbonic anhydrase and acid–base regulation in fish

“…Indeed, until the finding of CA-mediated SO 4 2-excretion (Renfro et al, 1999), it was believed that the kidney of marine fish lacked CA activity entirely. Although relatively few species have been examined, the available data derived from studies using isolated tubules or employing immunocytochemistry suggest that CA is present in the kidneys of both marine and freshwater fish (Renfro et al, 1999;Pelis et al, 2003;Pelis and Renfro, 2004;Georgalis et al, 2006a;Gilmour et al, 2007a). The predominant CA isoform in trout kidney is the general cytosolic variant (tCAc) (Esbaugh et al, 2005).…”

“…Osorezan dace (Hirata et al, 2003); winter flounder (Pleuronectes americanus) (Pelis et al, 2003)], this renal CA is probably more appropriately termed cytosolic CA ('c' or 'a' nomenclature; see above). In trout and flounder, cytosolic CA is found within proximal tubules where it immunolocalizes to the cytosol and brush border membranes (Pelis and Renfro, 2004;Georgalis et al, 2006a) (Fig. 6).…”

“…A vital participant in all three processes is carbonic anhydrase (CA), the zinc metalloenzyme that catalyses the reversible hydration/dehydration reactions of CO 2 and that therefore is critical to CO 2 excretion, ionic regulation and acid-base balance. The role played by CA in acid-base balance in fish often takes a backseat to its more visible roles in CO 2 excretion (for reviews, see Randall and Val, 1995;Henry and Heming, 1998;Tufts and Perry, 1998;Henry and Swenson, 2000;Tufts et al, 2003;Evans et al, 2005;Esbaugh and Tufts, 2006a) and ionic regulation (for reviews, see Maetz, 1971;Maetz and Bornancin, 1975;Haswell et al, 1980;Pelis and Renfro, 2004;Evans et al, 2005;Tresguerres et al, 2006a). Thus, the objective of this paper is to highlight the contributions of CA to acid-base regulation in fish and, keeping in mind previous reviews of acid-base regulation in fish that have touched upon CA (e.g.…”

Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

“…The strength of the Ussing chamber technique is that by eliminating the chemical (identical saline on both sides of the tissue) and electrical (voltage-clamped conditions) gradient across the tissue preparation, it allows for the determination of "active" transepithelial transport of solutes. The organic anions tested were 6-carboxyfluorescein, paraaminohippurate, and estrone-3-sulfate, all of which are substrates of OAT1 and/or OAT3 and are secreted by renal proximal tubules (Pelis and Renfro, 2004). Kondo and Araie (1994) showed a transport flux ratio (aqueous humor-to-blood flux/blood-to-aqueous humor flux) for 6-carboxyfluorescein (10 mM) of approximately 5 across the rabbit ciliary body.…”