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M Soleimani

Publications and source records attributed to M Soleimani.

At least 19 recordsLinked to original sources
PubMed2005

Guidelines for prevention and management of complications following kidney transplantation in rats.

Kidney transplantation in rats is a useful model for microsurgery, transplantation, and immunology studies. Our aim was to analyze various techniques of kidney transplantation in rats with emphasis on guidelines for the prevention and management of complications. Complications were categorized into general, vascular, and urological types and respectively attributed to long transplantation time, core body temperature drop, nonreplaced intraoperative blood loss, anastomosis failure, and ureteral anastomoses with stents or cannulas, which increase the risk of calculus formation. In conclusion, to decrease the complication rates the animal should be placed on a heating pad. For hemodynamic stability NaCl should be administered subcutaneously. To reduce the risk of thrombosis, ice-cold saline containing heparin should be administered. Vascular complications, which mainly depend on the microsurgeon's expertise, can be prevented by meticulous surgical technique (preferably an end-in-end anastomosis). The main urinary complications can be minimized by avoiding stents and cannulas and focusing on using techniques like the bladder-patch technique.

Animal Husbandry↗
PubMed2005

The effect of cryopreservation on clonogenic capacity and in vitro expansion potential of umbilical cord blood progenitor cells.

BACKGROUND: Umbilical cord blood progenitor cells have been demonstrated to possess significant advantages over bone marrow in terms of proliferative capacity and immunologic reactivity. But the low number of hematopoeitic stem cells (HSC) is the most important limitation of its use. The ex vivo expansion of cord blood progenitor cells is the current strategy to overcome this problem. Furthermore, among the factors that enable successful cord blood transplantation is the ability to store and subsequently recover a sufficient number of viable cells. Since it would be costly to expand umbilical cord blood (UCB) progenitor cells, it is important to determine the feasibility and reproducibility of progenitor cell expansion after cryopreservation. We evaluated whether cryopreservation procedures might impair the clonogenic capacity and in vitro expansion of UCB. MATERIALS AND METHODS: We evaluated the cell viability, clonogenic capacity, CD34+38- content and in vitro expansion potential of progenitor cells from UCB (n = 10) separated mononuclear cells (MNC), before and after 1 month of cryopreservation by programmed rate freezing. RESULTS: Although cell viability decreased after cryopreservation (P < .05), there was no significant difference in CD34+ or CD34+38- absolute count, colonogenic capacity and in vitro expansion potential of cord blood progenitor cells (P > .05). CONCLUSIONS: Since the survival of CD34+ cells was greater than other elements, CD34+ cells seem more tolerant to cryopreservation than the other nucleated populations. Moreover in vitro expansion of UCB progenitor cells may be obtained following cryopreservation. Our results suggest that cryopreservation procedures do not impair the clonogenic capacity and in vitro expansion potential of cord blood stem/progenitor cells.

ADP-ribosyl Cyclase 1↗
PubMed2003

Functional and molecular properties of Na+:HCO-3 cotransporters (NBC).

The sodium bicarbonate cotransporter (NBC) is located on the basolateral membrane of the kidney proximal tubule and is responsible for the reabsorption of the majority of filtered bicarbonate. In secretory epithelia (such as pancreatic duct) NBC is responsible for the transport of bicarbonate from the blood to the cell for the eventual secretion at the apical membrane. As such and due to its versatility, NBC can function in 2 distinct modes of bicarbonate reabsorption or secretion depending on the epithelia. NBC is also present in a wide variety of non-epithelial tissues where it is mainly involved with cell pH regulation. Recent molecular cloning experiments have identified the existence of 4 NBC isoforms (NBC1, 2, 3 and 4) and 2 NBC-related proteins AE4 and NCBE (anion exchanger 4 and sodium-dependent chloride-bicarbonate exchanger). Except for AE4 which does not transport Na, all are presumed to mediate the cotransport of Na+ and HCO(3)-. NBC isoforms show significant homology to each other and to the AE (anion exchange) family. NBC1 shows a limited tissue expression pattern, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. A variant of NBC1 is expressed in pancreatic duct and gastrointestinal tract, and plays an important role in HCO(3)- secretion. NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation. The electrogenecity of NBC4 may be variant-specific. An NBC related protein called NCBE mediates Na-dependent, Cl-/bicarbonate ex-change. The purpose of this review is to summarize functional and molecular properties of NBC isoforms and related proteins, and discuss their role and regulation in pathophysiologic states.

Acid-Base Imbalance↗
PubMed2001

Na+:HCO(3-) cotransporters (NBC): cloning and characterization.

The sodium bicarbonate cotransporter (NBC1) is essential for bicarbonate transport across plasma membranes in epithelial and nonepithelial cells. The direction of the NaHCO3 movement in secretory epithelia is opposite to that in reabsorptive epithelia. In secretory epithelia (such as pancreatic duct cells) NBC is responsible for the transport of bicarbonate from blood to the cell for eventual secretion at the apical membrane. In reabsorptive epithelia (such as kidney proximal tubule cells) NBC is responsible for the reabsorption of bicarbonate from cell to the blood. In nonepithelial cells this transporter is mainly involved with cell pH regulation. Recent molecular cloning experiments have identified the existence of four NBC isoforms (NBC1, 2, 3 and 4) and two NBC-related proteins AE4 and NCBE (Anion Exchanger 4 and Na-dependent Chloride-Bicarbonate Exchanger). All but AE4 are presumed to mediate the cotransport of Na+ and HCO(3-) under normal conditions and may be functionally altered in certain pathologic states. NBC1 shows a limited tissue expression pattern, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. In addition to the kidney, NBC1 is expressed in pancreatic duct cells, is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an important role in HCO3- secretion. NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation. The characterization of NBC4 is incomplete. The NBC-related protein called NCBE mediates Na-dependent, Cl-/Bicarbonate Exchange. The purpose of this review is to summarize recent advances on the cloning of NBC isoforms and related proteins and their role and regulation in physiologic and pathologic states.

Acid-Base Equilibrium↗
PubMed2001

Molecular and functional characterization of sodium--hydrogen exchanger in skin as well as cultured keratinocytes and melanocytes.

The sodium--hydrogen (Na(+)/H(+)) exchanger is one of the few transporter proteins involved in the regulation and maintenance of intracellular pH and cell volume in most eukaryotic cell types. The current study investigates the expression of isoforms of the Na(+)/H(+) exchanger (NHE) in human skin and in cultured keratinocytes, melanocytes, and melanoma cells by reverse transcription-polymerase chain reaction (RT--PCR), immunohistochemical analysis and functional studies. Neonatal foreskins were used to isolate RNA from epidermis and dermis, and to initiate cultures of keratinocytes and melanocytes. RT--PCR on RNA isolated from epidermis, dermis, keratinocytes, melanocytes and melanoma cells using PCR primers specific for NHE-1 yielded a 463 bp PCR product. RT--PCR performed using primers specific for NHE isoforms 2, 3, 4 and 5 did not yield any products. Western blotting analysis (of keratinocyte and melanocyte cell cultures) and indirect immunohistochemistry on neonatal foreskin, keratinocytes, melanocytes and melanoma cells using a NHE-1-specific polyclonal antibody demonstrated NHE-1 expression at the protein level. Physiological regulation of intracellular pH using a pH-sensitive dye, BCECF, detected an amiloride-sensitive NHE activity in human keratinocyte, melanocyte and melanoma cell cultures. These results indicate that cultures of human keratinocytes and melanocytes established from human skin and melanoma cells express the NHE-1 isoform of the sodium--hydrogen exchanger.

Cells, Cultured↗
PubMed2001

Coordinated down-regulation of NBC-1 and NHE-3 in sodium and bicarbonate loading.

BACKGROUND: Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in the kidney. METHODS: Rats were placed on 280 mmol/L of NaHCO(3), NaCl, or NH(4)Cl added to their drinking water for 5 days and examined for the expression of NHE-3 and NBC-1 in the kidney. RESULTS: Serum [HCO(-3)] was unchanged in NaHCO(-3) and NaCl-loaded animals versus control (P> 0.05). However, a significant hyperchloremic metabolic acidosis was developed in NH4Cl-loaded animals. A specific polyclonal antibody against NBC-1 recognized a 130 kD band, which was exclusively expressed in the basolateral membrane of proximal tubules. Immunoblot studies indicated that the protein abundance of NBC-1 and NHE-3 in the cortex decreased by 74% (P < 0.04) and 66% (P < 0.03), respectively, in NaHCO(3) loading and by 72% (P < 0.003) and 55% (P < 0.04), respectively, in NaCl loading. Switching from NaHCO(3) to distilled water resulted in rapid recovery of NHE-3 and NBC-1 protein expression toward normal levels. Metabolic acidosis increased the abundance of NHE-3 (P < 0.0001) but not NBC-1 (P> 0.05). CONCLUSIONS: NaHCO(-3) or NaCl loading coordinately down-regulates the apical NHE-3 and basolateral NBC-1 in rat kidney proximal tubule, presumably due to increased Na+ load. We propose that the down-regulation of these two Na+- and HCO(3)-absorbing transporters is, to a large degree, responsible for enhanced excretion of excess of Na+ and alkaline load and prevention of metabolic alkalosis in rats subjected to NaHCO(-3) loading.

Animals↗
PubMed2001

Mouse Na+: HCO3- cotransporter isoform NBC-3 (kNBC-3): cloning, expression, and renal distribution.

BACKGROUND: Na+:HCO3- cotransporters mediate the transport of HCO3- into or out of the cell. We recently reported the partial cloning and characterization of a new human Na+:HCO3- cotransporter (referred to as NBC-3 or kNBC-3). The purpose of the present studies was to clone the mouse kNBC-3 and to examine its properties and expression in the kidney. METHODS: Using primers from human kNBC-3 cDNA and 5' and 3' rapid amplification cDNA end polymerase chain reaction (RACE PCR), the mouse kNBC-3 full-length cDNA was cloned from inner medullary collecting duct (mIMCD-3) cells. The tissue distribution and functional properties of NBC-3 was determined using established methods. RESULTS: The coding region of the mouse kNBC-3 has 1089 amino acids and shows 73 and 56% identity to human NBC-2 and NBC-1, respectively. The renal distribution of kNBC-3 demonstrated a unique expression pattern: Whereas kNBC-1 is predominantly expressed in the cortex and is absent in the inner medulla, kNBC-3 shows an intense expression level in the inner medulla and is absent in the cortex. Expression studies in oocytes indicated that NBC-3 mediates Na-dependent HCO3- cotransport. Electrophysiological experiments demonstrated that unlike kNBC-1, which is electrogenic, kNBC-3 is electroneutral. CONCLUSIONS: Based on its distribution and electroneutrality, we propose that kNBC-3 mediates the transport of HCO3- into the cells.

Amino Acid Sequence↗
PubMed2001

Molecular physiology of the renal chloride-formate exchanger.

Renal apical chloride-base exchangers are essential to electrolyte and acid-base homeostasis. Different functional isoforms of apical anion exchangers have been identified in kidney proximal tubule and cortical collecting duct. Included amongst these are the following: chloride-formate, chloride-oxalate, and chloride-hydroxyl exchangers in proximal tubule; and chloride-bicarbonate exchanger in cortical collecting duct. Chloride-formate exchange, which was first identified in kidney proximal tubule, works in parallel with the apical sodium-hydrogen exchanger, and is thought to reabsorb the bulk of luminal chloride. Despite numerous studies, the molecular identities of apical chloride-base exchangers have remained unknown. Recent studies have identified a new class of anion exchangers, including pendrin (encoded by the PDS gene) and downregulated in adenoma (DRA, encoded by the DRA gene). Pendrin is expressed in the kidney, whereas DRA is not. Functional studies indicate that pendrin can function in chloride-formate and chloride-base exchange modes. It is unlikely that pendrin is the apical chloride-formate exchanger in the kidney proximal tubule. However, it is the only molecule that has been shown to mediate chloride-formate exchange. In the present review, recent studies regarding the renal distribution and membrane localization of pendrin, and its functional properties, including its roles in chloride reabsorption and base excretion, are addressed.

Animals↗
PubMed2001

Hypokalaemia and hyperkalaemia.

Disturbances in potassium homoeostasis presenting as low or high serum potassium are common, especially among hospitalised patients. Given the fact that untreated hypokalaemia or hyperkalaemia is associated with high morbidity and mortality, it is critical to recognise and treat these disorders promptly. In this article, normal potassium homoeostasis is reviewed initially and then a pathophysiological approach to work-up and management of hypokalaemia and hyperkalaemia is presented. Recent advances with respect to the role of kidney in handling of the potassium, the regulation of renal ion transporters in hypokalaemia, and treatment of hypokalaemia and hyperkalaemia will be discussed.

Hemostasis↗
PubMed2001

Downregulated in adenoma and putative anion transporter are regulated by CFTR in cultured pancreatic duct cells.

The mechanism of the pancreatic ductal HCO secretion defect in cystic fibrosis (CF) is not well defined. However, a lack of apical Cl(-)/HCO exchange may exist in CF. To test this hypothesis, we examined the expression of Cl(-)/HCO exchangers in cultured pancreatic duct epithelial cells with physiological features prototypical of CF [CFPAC-1 cells lacking a functional CF transmembrane conductance regulator (CFTR)] or normal duct cells (CFPAC-1 cells transfected with functional wild-type CFTR, CFPAC-WT). Cl(-)/HCO exchange activity, assayed with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in cells grown on coverslips, increased about twofold in cells transfected with functional CFTR. This correlated with increased apical (36)Cl influx in cells expressing functional CFTR and grown on permeable support. Northern hybridizations indicated the induction of downregulated in adenoma (DRA) in cells expressing functional CFTR. The expression of putative anion transporter PAT1 also increased significantly in cells expressing functional CFTR. DRA was detected at high levels in native mouse pancreas by Northern hybridization and localized to the apical domain of the duct cells by immunohistochemical studies. In conclusion, CFTR upregulates DRA and PAT1 expression in cultured pancreatic duct cells. We propose that the pancreatic HCO secretion defect in CF patients is partly due to the downregulation of apical Cl(-)/HCO exchange activity mediated by DRA (and possibly PAT1).

Animals↗
PubMed2001

Pendrin: an apical Cl-/OH-/HCO3- exchanger in the kidney cortex.

The identities of the apical Cl-/base exchangers in kidney proximal tubule and cortical collecting duct (CCD) cells remain unknown. Pendrin (PDS), which is expressed at high levels in the thyroid and its mutation causes Pendred's syndrome, is shown to be an anion exchanger. We investigated the renal distribution of PDS and its function. Our results demonstrate that pendrin mRNA expression in the rat kidney is abundant and limited to the cortex. Proximal tubule suspensions isolated from kidney cortex were highly enriched in pendrin mRNA. Immunoblot analysis studies localized pendrin to cortical brush-border membranes. Nephron segment RT-PCR localized pendrin mRNA to proximal tubule and CCD. Expression studies in HEK-293 cells demonstrated that pendrin functions in the Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange modes. The conclusion is that pendrin is an apical Cl-/base exchanger in the kidney proximal tubule and CCD and mediates Cl-/OH-, Cl-/HCO3-, and Cl-/formate exchange.

Analysis of Variance↗
PubMed2001

Fasting downregulates renal water channel AQP2 and causes polyuria.

Starvation causes impairment in the urinary concentrating ability. The mechanism of this defect, however, remains unknown. We tested the possibility that food deprivation might affect the expression and activity of aquaporins (AQP1, 2), thereby impairing renal water reabsorption in the kidney. Rats fasted for 24 h exhibited severe polyuria (urine volume increased from 11 before fasting to 29 ml/24 h after fasting, P < 0.0001) along with failure to concentrate their urine (urine osmolality decreased from 1,485 before fasting to 495 mosmol/kgH(2)O after fasting, P < 0.0001). Refeeding for 24 h returned the urinary concentrating ability back to normal. Northern hybridization and immunoblot analysis demonstrated that fasting was associated with a decrease in AQP2 protein (-80%, P </= 0.002) and mRNA levels (-69%, P </= 0.003) in the outer medulla. In the cortex, fasting decreased AQP2 protein abundance by 60% (P </= 0.004) but did not alter its mRNA expression. During the recovery phase, AQP2 expression returned to normal level in both tissues. In the inner medulla, the expression of AQP2 was not altered in fasting, but was increased significantly at both protein ( +/- 92%) and mRNA ( +/- 43%) levels during the recovery from fasting. The proximal nephron water channel (AQP1) was not affected in response to fasting or recovery from fasting. We conclude that 1) fasting impairs the urinary concentrating ability in rats, and 2) the renal water-handling defect in fasting results specifically from the downregulation of AQP2 in the cortical and outer medullary collecting duct.

Animals↗
PubMed2001

Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2.

To study the role of Na+/H+ exchanger isoform 2 (NHE2) and isoform 3 (NHE3) in sodium-fluid volume homeostasis and renal Na+ conservation, mice with Nhe2 (Nhe2-/-) and/or Nhe3 (Nhe3-/-) null mutations were fed a Na+-restricted diet, and urinary Na+ excretion, blood pressure, systemic acid-base and electrolyte status, and renal function were analyzed. Na+ -restricted Nhe2-/- mice, on either a wild-type or Nhe3 heterozygous mutant (Nhe3+/-) background, did not exhibit excess urinary Na+ excretion. After 15 days of Na+ restriction, blood pressure, fractional excretion of Na+, and the glomerular filtration rate (GFR) of Nhe2-/-Nhe3+/- mice were similar to those of Nhe2+/+ and Nhe3+/- mice, and no metabolic disturbances were observed. Nhe3-/- mice maintained on a Na+-restricted diet for 3 days exhibited hyperkalemia, urinary salt wasting, acidosis, sharply reduced blood pressure and GFR, and evidence of hypovolemic shock. These results negate the hypothesis that NHE2 plays an important renal function in sodium-fluid volume homeostasis; however, they demonstrate that NHE3 is critical for systemic electrolyte, acid-base, and fluid volume homeostasis during dietary Na+ restriction and that its absence leads to renal salt wasting.

Acid-Base Equilibrium↗
PubMed2001

Impaired pancreatic ductal bicarbonate secretion in cystic fibrosis.

Patients with cystic fibrosis demonstrate a defect in HCO(3)(-) secretion by their pancreatic duct cells. However, attempts toward understanding or correcting this defect have been hampered by a lack of knowledge regarding the cellular and molecular mechanisms mediating HCO(3)(-) transport in these cells. Recent functional and molecular studies indicate a major role for a basolateral electrogenically-driven Na(+):HCO(3)(-) cotransporter (NBC1) in mediating the transport of HCO(3)(-) into the duct cells. The HCO(3)(-) exits at the lumen predominantly via two recently discovered apical HCO(3)(-) transporters. cAMP, which mediates the stimulatory effect of secretin on pancreatic ductal HCO(3)(-) secretion, potentiates the basolateral Na(+):HCO(3)(-) cotransporter due to generation of a favorable electrogenic gradient as a result of membrane depolarization by Cl(-)-secreting cystic fibrosis transmembrane conductance regulator (CFTR). Two apical HCO(3)(-) transporters drive the secretion of bicarbonate into the pancreatic duct lumen. Molecular and functional studies indicate that CFTR upregulates the expression of these two apical HCO(3)(-) transporters. In addition, CFTR may also upregulate the expression of certain water channels and facilitate the secretion of fluid into the duct lumen. In brief, current research suggests that the defect in pancreatic HCO(3)(-) secretion in patients with cystic fibrosis is multifactorial and involves the alteration in the function/expression of transporters at the basolateral and luminal membrane domains of the duct cells.

Bicarbonates↗
PubMed2000

Possible molecular basis for changes in potassium handling in acute renal failure.

Renal potassium excretion is diminished in acute renal failure (ARF). The gastrointestinal tract can compensate for deficient renal potassium excretion in many patients with ARF. For both impaired renal potassium excretion and gastrointestinal compensation in ARF, little is known about the role of potassium channels. We hypothesized that specific changes in the expression of the secretory renal outer medullary potassium channel (ROMK), and the potassium channel regulator, channel-inducing factor (CHIF), in kidney and colon could contribute to changes in potassium handling. Sprague-Dawley rats underwent uninephrectomy and 35 minutes of renal ischemia, followed by varying periods of reperfusion. Renal function, serum and urine potassium levels, and aldosterone levels were measured. The expression of messenger RNA (mRNA) for ROMK and CHIF in the kidney and CHIF in the colon were measured by Northern blot hybridization. Serum creatinine level was increased at 24 hours and started to decline at 48 hours of renal ischemia reperfusion injury (IRI). Serum potassium level was increased at 24 hours, further elevated at 48 hours of IRI, and returned to normal at 7 days of IRI. Urine potassium level was reduced at 24 and 48 hours. Northern blot analysis indicated that the expression of ROMK1 mRNA in the cortex or medulla remained unchanged at 24 hours but profoundly decreased (by 70% to 80%) at 48 hours (n = 4; P < 0.01). The expression of CHIF mRNA in the kidney cortex or medulla decreased by 25% to 30% at 24 hours and 35% to 40% at 48 hours of IRI (n = 4; P < 0.05 for each group). CHIF mRNA expression in the distal colon was moderately increased at 24 hours (approximately twofold) and significantly enhanced at 48 hours (more than threefold; P < 0.01; n = 4) of IRI. Serum aldosterone level was increased approximately threefold at 48 hours of IRI (P < 0.01; n = 6). In conclusion, (1) suppression of ROMK and CHIF in the kidney may contribute to decreased renal potassium excretion in ARF; (2) enhanced expression of CHIF in the distal colon in IRI could be an adaptive response to increase potassium excretion in the colon and help modify hyperkalemia in ARF; and (3) increased aldosterone levels, as a response to hyperkalemia, could be upregulating colonic CHIF.

Acute Kidney Injury↗
PubMed2000

Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.

Approximately 80% of the filtered load of HCO3- is reabsorbed in the proximal tubule via a process of active acid secretion by the luminal membrane. The major mechanism for the transport of HCO3- across the basolateral membrane is via the electrogenic Na+:3HCO3- cotransporter (NBC). Recent molecular cloning experiments have identified the existence of three NBC isoforms (NBC-1, NBC-2, and NBC-3).1 Functional and molecular studies indicate the presence of all three NBC isoforms in the kidney. All are presumed to mediate the cotransport of Na+ and HCO3- under normal conditions and may be functionally altered in certain pathophysiologic states. Specifically, NBC-1 may be up-regulated in metabolic acidosis and potassium depletion and in response to glucocorticoid excess and may be down-regulated in response to HCO3- loading or alkalosis. Recent studies provide molecular evidence indicating the expression of NBC-1 in pancreatic duct cells. NBC is activated by cystic fibrosis transmembrane conductance regulator (CFTR) and plays an important role in HCO3- secretion in the agonist-stimulated state in pancreatic duct cells. The purpose of this review is to summarize recent functional and molecular studies on the regulation of NBCs in physiologic and pathophysiologic states. Possible signals responsible for the regulation of NBCs in these conditions are examined. Furthermore, the possible role of this transporter in acid-base disorders (such as proximal renal tubular acidosis) is discussed.

Animals↗
PubMed2000

Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules.

BACKGROUND: Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H(+)-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- cotransporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules. METHODS: Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules. RESULTS: Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pHi recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs. control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression. CONCLUSION: Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.

Animals↗