Collecting duct function in cis-platinum nephrotoxicity

1987 ◽  
Vol 65 (6) ◽  
pp. 1200-1204 ◽  
Author(s):  
Douglas R. Wilson ◽  
Ursula Honrath
Keyword(s):  
Sodium Chloride ◽  
Collecting Duct ◽  
Chloride Concentration ◽  
Water Reabsorption ◽  
Pars Recta ◽  
Anaesthetized Rats ◽  
Medullary Collecting Duct ◽  
In Cis ◽  
Tissue Sodium ◽  
Urine Concentrating Ability

Microcatheterization was used to study the effect of cis-platinum nephrotoxicity on inner medullary collecting duct function in anaesthetized rats. Osmolality of collecting duct fluid increased from the beginning to the end (papillary tip) of the collecting duct by only 69 ± 11 mosmol/kg in cis-platinum treated rats (at 5–6 days) compared with 306 ± 75 mosmol/kg in sham controls (p < 0.01). Tubular fluid to plasma inulin concentration ratio was reduced at the beginning and end of the collecting duct. Tubular fluid sodium, chloride, and potassium concentrations were lower at the papillary tip in cis-platinum treated rats (p < 0.01). The results indicate that collecting duct water reabsorption is reduced, but electrolyte reabsorption is normal (or even increased) in cis-platinum nephrotoxicity. Papillary tissue sodium chloride concentration was reduced in cis-platinum treated rats. We conclude that the characteristic decrease in urine concentrating ability in cis-platinum nephrotoxicity is not primarily the result of an intrinsic abnormality in collecting duct function but is secondary to decreased papillary hypertonicity resulting from impaired function in more proximal nephron segments, presumably the pars recta of the proximal tubule and the loop of Henle where previous studies have demonstrated abnormal function.

Effects of increased perfusion pressure on medullary collecting duct function

1990 ◽  
Vol 68 (3) ◽  
pp. 402-407 ◽  
Author(s):  
H. Sonnenberg ◽  
U. Honrath ◽  
D. R. Wilson
Keyword(s):  
Sodium Chloride ◽  
Perfusion Pressure ◽  
Collecting Duct ◽  
Time Control ◽  
Bilateral Carotid ◽  
Anaesthetized Rats ◽  
Acute Increase ◽  
Medullary Collecting Duct ◽  
Pressure Natriuresis

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 ± 4.1 to 51 ± 9.3% (p < 0.01) and from 65.7 ± 6.0 to 42.7 ± 9.1% (p < 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.Key words: hypertension, vagotomy, collecting duct, sodium excretion, atrial natriuretic factor.

scholarly journals Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts

2019 ◽  
Vol 316 (2) ◽  
pp. F253-F262 ◽  
Author(s):  
Josephine K. Liwang ◽  
Joseph A. Ruiz ◽  
Lauren M. LaRocque ◽  
Fitra Rianto ◽  
Fuying Ma ◽  
...  
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Adenosine Monophosphate ◽  
Osmotic Water Permeability ◽  
Water Reabsorption ◽  
Compound C ◽  
Ampk Phosphorylation ◽  
Osmotic Water ◽  
Medullary Collecting Duct

Hypertonicity increases water permeability, independently of vasopressin, in the inner medullary collecting duct (IMCD) by increasing aquaporin-2 (AQP2) membrane accumulation. We investigated whether protein kinase C (PKC) and adenosine monophosphate kinase (AMPK) are involved in hypertonicity-regulated water permeability. Increasing perfusate osmolality from 150 to 290 mosmol/kgH2O and bath osmolality from 290 to 430 mosmol/kgH2O significantly stimulated osmotic water permeability. The PKC inhibitors chelerythrine (10 µM) and rottlerin (50 µM) significantly reversed the increase in osmotic water permeability stimulated by hypertonicity in perfused rat terminal IMCDs. Chelerythrine significantly increased phosphorylation of AQP2 at S261 but not at S256. Previous studies show that AMPK is stimulated by osmotic stress. We tested AMPK phosphorylation under hypertonic conditions. Hypertonicity significantly increased AMPK phosphorylation in inner medullary tissues. Blockade of AMPK with Compound C decreased hypertonicity-stimulated water permeability but did not alter phosphorylation of AQP2 at S256 and S261. AICAR, an AMPK stimulator, caused a transient increase in osmotic water permeability and increased phosphorylation of AQP2 at S256. When inner medullary tissue was treated with the PKC activator phorbol dibutyrate (PDBu), the AMPK activator metformin, or both, AQP2 phosphorylation at S261 was decreased with PDBu or metformin alone, but there was no additive effect on phosphorylation with PDBu and metformin together. In conclusion, hypertonicity regulates water reabsorption by activating PKC. Hypertonicity-stimulated water reabsorption by PKC may be related to the decrease in endocytosis of AQP2. AMPK activation promotes water reabsorption, but the mechanism remains to be determined. PKC and AMPK do not appear to act synergistically to regulate water reabsorption.

Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney

1995 ◽  
Vol 269 (4) ◽  
pp. F461-F468 ◽  
Author(s):  
F. C. Brosius ◽  
K. Nguyen ◽  
A. K. Stuart-Tilley ◽  
C. Haller ◽  
J. P. Briggs ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Chloride Concentration ◽  
Transepithelial Transport ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Base Exchange ◽  
Medullary Thick Ascending Limb ◽  
Nephron Segment ◽  
Medullary Collecting Duct

Chloride/base exchange activity has been detected in every mammalian nephron segment in which it has been sought. However, in contrast to the Cl-/HCO3- exchanger AE1 in type A intercalated cells, localization of AE2 within the kidney has not been reported. We therefore studied AE2 expression in rat kidney. AE2 mRNA was present in cortex, outer medulla, and inner medulla. Semiquantitative polymerase chain reaction of cDNA from microdissected tubules revealed AE2 cDNA levels as follows [copies of cDNA derived per mm tubule (+/- SE)]: proximal convoluted tubule, 688 +/- 161; proximal straight tubule, 652 +/- 189; medullary thick ascending limb, 1,378 +/- 226; cortical thick ascending limb, 741 +/- 24; cortical collecting duct, 909 +/- 71; and outer medullary collecting duct, 579 +/- 132. AE2 cDNA was also amplified in thin limbs and in inner medullary collecting duct. AE2 polypeptide was detected in all kidney regions. AE2 mRNA and protein were also detected in several renal cell lines. The data are compatible with the postulated roles of AE2 in maintenance of intracellular pH and chloride concentration and with its possible participation in transepithelial transport.

scholarly journals Adrenomedullin Inhibits Osmotic Water Permeability in Rat Inner Medullary Collecting Ducts

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2533
Author(s):  
Fuying Ma ◽  
Guangping Chen ◽  
Eva L. Rodriguez ◽  
Janet D. Klein ◽  
Jeff M. Sands ◽  
...  
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Osmotic Water Permeability ◽  
Water Reabsorption ◽  
Kinase C ◽  
Osmotic Water ◽  
Collecting Ducts ◽  
Medullary Collecting Duct ◽  
Camp Levels ◽  
Reduced Water

Adrenomedullin (ADM) is a vasodilator that causes natriuresis and diuresis. However, the direct effect of ADM on osmotic water permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether ADM and its ADM receptor components (CRLR, RAMP2, and 3) are expressed in rat inner medulla (IM) and whether ADM regulates osmotic water permeability in isolated perfused rat IMCDs. The mRNAs of ADM, CRLR, and RAMP2 and 3 were detected in rat IM. Abundant protein of CRLR and RAMP3 were also seen but RAMP2 protein level was extremely low. Adding ADM (100 nM) to the bath significantly decreased osmotic water permeability. ADM significantly decreased aquaporin-2 (AQP2) phosphorylation at Serine 256 (pS256) and increased it at Serine 261 (pS261). ADM significantly increased cAMP levels in IM. However, inhibition of cAMP by SQ22536 further decreased ADM-attenuated osmotic water permeability. Stimulation of cAMP by roflumilast increased ADM-attenuated osmotic water permeability. Previous studies show that ADM also stimulates phospholipase C (PLC) pathways including protein kinase C (PKC) and cGMP. We tested whether PLC pathways regulate ADM-attenuated osmotic water permeability. Blockade of either PLC by U73122 or PKC by rottlerin significantly augmented the ADM-attenuated osmotic water permeability and promoted pS256-AQP2 but did change pS261-AQP2. Inhibition of cGMP by L-NAME did not change AQP2 phosphorylation. In conclusion, ADM primarily binds to the CRLR-RAMP3 receptor to initiate signaling pathways in the IM. ADM reduced water reabsorption through a PLC-pathway involving PKC. ADM-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. cAMP is not involved in ADM-attenuated osmotic water permeability.

scholarly journals Proteomic determination of the lysine acetylome and phosphoproteome in the rat native inner medullary collecting duct

2018 ◽  
Vol 50 (9) ◽  
pp. 669-679 ◽  
Author(s):  
Kelly A. Hyndman ◽  
Chin-Rang Yang ◽  
Hyun Jun Jung ◽  
Ezigbobiara N. Umejiego ◽  
Chung-Ling Chou ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Collecting Duct ◽  
Water Channel ◽  
Receptor Activation ◽  
Phosphorylation Sites ◽  
Water Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Phosphorylated Proteins ◽  
V2 Receptor ◽  
Medullary Collecting Duct

Phosphorylation and lysine (K)-acetylation are dynamic posttranslational modifications of proteins. Previous proteomic studies have identified over 170,000 phosphorylation sites and 15,000 K-acetylation sites in mammals. We recently reported that the inner medullary collecting duct (IMCD), which functions in the regulation of water-reabsorption, via the actions of vasopressin, expresses many of the enzymes that can modulated K-acetylation. The purpose of this study was to determine the K-acetylated or phosphorylated proteins expressed in IMCD cells. Second we questioned whether vasopressin V2 receptor activation significantly affects the IMCD acetylome or phosphoproteome? K-acetylated or serine-, threonine-, or tyrosine-phosphorylated peptides were identified from native rat IMCDs by proteomic analysis with four different enzymes (trypsin, chymotrypsin, ASP-N, or Glu-C) to generate a high-resolution proteome. K-acetylation was identified in 431 unique proteins, and 64% of the K-acetylated sites were novel. The acetylated proteins were expressed in all compartments of the cell and were enriched in pathways including glycolysis and vasopressin-regulated water reabsorption. In the vasopressin-regulated water reabsorption pathway, eight proteins were acetylated, including the novel identification of the basolateral water channel, AQP3, acetylated at K282; 215 proteins were phosphorylated in this IMCD cohort, including AQP2 peptides that were phosphorylated at four serines: 256, 261, 264, and 269. Acute dDAVP did not significantly affect the IMCD acetylome; however, it did significantly affect previously known vasopressin-regulated phosphorylation sites. In conclusion, presence of K-acetylated proteins involved in metabolism, ion, and water transport in the IMCD points to multiple roles of K-acetylation beyond its canonical role in transcriptional regulation.

Renal medullary plasma flow rate and reabsorption of salt and water from inner medullary collecting duct

1987 ◽  
Vol 65 (12) ◽  
pp. 2415-2421 ◽  
Author(s):  
W. A. Cupples ◽  
H. Sonnenberg
Keyword(s):  
Blood Flow ◽  
Sodium Chloride ◽  
Angiotensin Ii ◽  
Flow Rate ◽  
Plasma Flow ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Renal Circulation ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct

It has been proposed that medullary washout secondary to increased blood flow will limit maximal urine osmolality and reabsorption of salt and water from the inner medullary collecting duct. We have tested this prediction. The function of the inner medullary collecting duct was examined by microcatheterization. Acetylcholine was infused directly into the renal circulation, captopril was infused intravenously, and angiotensin II was infused into the renal circulation in rats which also received captopril. Medullary plasma flow rate, measured by dye–dilution in parallel experiments, was not significantly increased by acetylcholine; it was increased 30% (p < 0.02) by systemic infusion of captopril, and was returned to control by angiotensin II. Acetylcholine increased both urine flow rate and sodium excretion (p < 0.01, p < 0.001, respectively), while captopril increased only sodium excretion (p < 0.025). Angiotensin II blocked the natriuresis due to captopril. None of the treatments altered urine osmolality (p > 0.4 in all cases). Acetylcholine increased the loads of water, sodium, chloride, and total solute delivered to the inner medullary collecting duct. Angiotensin II reduced delivery of water and solutes compared with captopril alone. None of the treatments affected load dependency of reabsorption of water, sodium, chloride, or total solute in the inner medullary collecting duct. We conclude that there is, at most, a weak interaction between medullary blood flow and reabsorption from the inner medullary collecting duct.

Sodium and chloride transport along the inner medullary collecting duct: effect of saline expansion

1980 ◽  
Vol 238 (6) ◽  
pp. F504-F508 ◽  
Author(s):  
H. H. Bengele ◽  
C. Lechene ◽  
E. A. Alexander
Keyword(s):  
Sodium Chloride ◽  
Sodium Transport ◽  
Volume Expansion ◽  
Chloride Transport ◽  
Collecting Duct ◽  
Urine Flow ◽  
Fluid Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Chloride Excretion ◽  
Medullary Collecting Duct

The effect of volume expansion on inner medullary collecting duct (IMCD) sodium transport remains controversial. Studies employing micropuncture of the IMCD base and tip were interpreted to demonstrate enhanced sodium and chloride reabsorption. Data obtained by microcatheterization evaluating only sodium transport revealed either no reabsorption or net addition. We have examined both sodium and chloride transport by microcatheterization. Volume expansion was comparable to the micropuncture studies: 0.9% saline equal to 10% body wt and then matched to urine flow. The fraction of filtered fluid, sodium, and chloride was analyzed as a function of IMCD length. In eight hydropenic rats 60% of the fluid, 71% of the sodium, and 48% of the chloride delivered to the IMCD was reabsorbed. In six volume-expanded rats no significant net reabsorption of fluid, sodium, or chloride was found. Accordingly, in contrast to the micropuncture results, we have demonstrated that net sodium chloride and fluid reabsorption are absent during volume expansion. We conclude that during volume expansion, fluid, sodium, and chloride excretion increase, in part, because of a reduction in net reabsorption along the IMCD. The degree of volume expansion does not account for the discrepancy between the two techniques.

scholarly journals Urea transport processes are induced in rat IMCD subsegments when urine concentrating ability is reduced

1999 ◽  
Vol 276 (1) ◽  
pp. F62-F71 ◽  
Author(s):  
Akihiko Kato ◽  
Jeff M. Sands
Keyword(s):  
Collecting Duct ◽  
Urine Concentration ◽  
Transport Processes ◽  
Urea Transport ◽  
Urea Transporter ◽  
Water Diuresis ◽  
Low Protein ◽  
Urea Reabsorption ◽  
Medullary Collecting Duct ◽  
Urine Concentrating Ability

Infusing urea into low-protein-fed mammals increases urine concentration within 5–10 min. To determine which urea transporter may be responsible, we measured urea transport in perfused IMCD3 segments [inner medullary collecting duct (IMCD) segments from the deepest third of the IMCD] from low-protein-fed rats. Basal facilitated urea permeability increased 78%, whereas active urea secretion was completely inhibited. This suggests that upregulation of facilitated urea transport may mediate the rapid increase in urine concentration. Next, expression of active urea transporter(s) in perfused IMCDs was determined in rats with other causes of reduced urine concentrating ability. In untreated and water diuretic rats, IMCD1 segments showed no active urea transport, nor did IMCD2segments from untreated or hypercalcemic rats. In IMCD1 segments from hypercalcemic rats, active urea reabsorption was induced. The induced active urea reabsorption was completely inhibited by replacing perfusate Na+ with N-methyl-d-glucamine (NMDG+). Active urea secretion was completely inhibited in IMCD3 segments from hypercalcemic rats. In contrast, water diuresis stimulated active urea secretion in IMCD2 segments. The induced active urea secretion was inhibited by phloretin, ouabain, triamterene, or replacing perfusate Na+ with NMDG+. In conclusion, the response of active urea transporters to reductions in urine concentrating ability follows two paradigms: one occurs with hypercalcemia or a low-protein diet, and the second occurs only in water diuresis.

Effect of adrenal enucleation on inner medullary collecting duct function in the rat

1982 ◽  
Vol 242 (5) ◽  
pp. F453-F456
Author(s):  
H. H. Bengele ◽  
E. A. Alexander
Keyword(s):  
Sodium Chloride ◽  
Collecting Duct ◽  
Potassium Excretion ◽  
Collection Site ◽  
Salt Load ◽  
Inner Medullary Collecting Duct ◽  
Impaired Ability ◽  
Potassium Secretion ◽  
Medullary Collecting Duct ◽  
And Control

After adrenal enucleation rats have an impaired ability to excrete a salt load. From micropuncture studies comparing data obtained from the late distal collection site and the urine, it has been suggested that this antinatriuretic effect occurs along the collecting duct. These studies are indirect, however, and cannot evaluate the contribution of deep nephrons. We have performed studies directly measuring inner medullary collecting duct (IMCD) function in saline-loaded rats 6 days after adrenal enucleation (AE). The fraction of filtered fluid, sodium, chloride, and potassium was analyzed as a function of IMCD length. In six AE rats 35% of the fluid, 35% of the sodium, and 31% of the chloride delivered to the IMCD was reabsorbed. In six saline-loaded control rats, however, no statistically significant net reabsorption of fluid sodium, or chloride was detected. Net potassium secretion along the IMCD was found in both AE and control rats. No difference between groups was noted, and net addition accounted for 17% of the potassium excreted. We conclude that after AE, the excretion of fluid, sodium, and chloride is impaired during saline expansion because of enhanced reabsorption along the IMCD. AE does not affect potassium handling along the IMCD or potassium excretion.

Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition

1983 ◽  
Vol 244 (6) ◽  
pp. F666-F673 ◽  
Author(s):  
D. R. Wilson ◽  
U. Honrath ◽  
H. Sonnenberg
Keyword(s):  
Collecting Duct ◽  
Prostaglandin Synthesis ◽  
Water Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Nephron Segments ◽  
Inhibit Prostaglandin Synthesis ◽  
Collecting Ducts ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Medullary Collecting Duct ◽  
Furosemide Administration

The effect of furosemide on inner medullary collecting duct chloride reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of chloride, sodium, and water reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamate before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis, and diuresis. Reduced delivery of sodium and chloride to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. The results indicate that furosemide inhibits medullary collecting duct reabsorption of chloride, sodium, and water in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.

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