Adaptation of inner medullary collecting duct to dehydration involves a paracellular pathway

1995 ◽  
Vol 268 (1) ◽  
pp. F53-F63 ◽  
Author(s):  
B. Flamion ◽  
K. R. Spring ◽  
M. Abramow
Keyword(s):  
Water Permeability ◽  
Apical Membrane ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Osmotic Water Permeability ◽  
Inner Medullary Collecting Duct ◽  
Osmotic Water ◽  
Medullary Collecting Duct ◽  
Paracellular Pathways

Prolonged fluid restriction in rats is accompanied by functional modifications of the terminal part of the inner medullary collecting duct (IMCD) revealed by a sustained increase in arginine vasopressin (AVP)-independent transepithelial osmotic water permeability (PTE) in vitro. The cellular basis of this adaptation was explored in isolated and perfused terminal IMCDs of Sprague-Dawley rats using video and fluorescence microscopy. Basolateral membrane osmotic water permeability (Posm), transcellular Posm, and PTE were measured in quick sequence in every tubule. They were expressed per unit area of basolateral membrane corrected for infoldings, based on previous stereological studies and assuming no major change in membrane surface area between hydrated and dehydrated animals. Compared with IMCDs of rats with a high water intake, IMCDs of rats deprived of fluid for 36 h displayed a significantly higher basal PTE (24.9 +/- 5.1 vs. 6.1 +/- 0.6 microns/s), a similar basolateral Posm, and a higher transcellular Posm, implying a higher permeability of the apical membrane, despite the absence of exogenous AVP. However, when IMCDs of thirsted rats were exposed to AVP in vitro, their transcellular Posm (36.0 +/- 2.4 microns/s) was significantly smaller than their PTE determined simultaneously (51.8 +/- 7.1 microns/s), suggesting that part of the water flow may follow a paracellular route. A change in paracellular pathways was supported by higher apparent permeabilities to [14C]sucrose (0.85 +/- 0.27 vs. 0.28 +/- 0.04 x 10(-5) cm/s) and to [methoxy-3H]inulin (0.25 +/- 0.04 vs. 0.14 +/- 0.03 x 10(-5) cm/s) in IMCDs of thirsted rats. The nonelectrolyte permeabilities were affected neither by AVP nor by urea-rich bathing solutions. We conclude that in vivo factors related to dehydration produce a conditioning effect on terminal IMCD, which includes stabilization of the apical membrane in a state of high Posm and opening up of paracellular pathways revealed by a higher permeability to water and nonelectrolytes. The role of these adaptive phenomena remains unclear but may pertain to the sudden transitions between antidiuresis and diuresis.

Regulation of osmotic water permeability during differentiation of inner medullary collecting duct

1991 ◽  
Vol 260 (5) ◽  
pp. F710-F716 ◽  
Author(s):  
E. Siga ◽  
M. F. Horster
Keyword(s):  
Water Permeability ◽  
Epithelial Transport ◽  
Collecting Duct ◽  
Osmotic Water Permeability ◽  
Osmotic Concentration ◽  
Inner Medullary Collecting Duct ◽  
Osmotic Water ◽  
Nephron Segment ◽  
Medullary Collecting Duct

Urinary osmotic concentration capacity during renal ontogeny is subject to changes of medullary cytoarchitecture and of segmental epithelial transport characteristics. Osmotic equilibrium between interstitial and tubular fluid of the terminal nephron segment in response to vasopressin is an absolute essential of maximal urinary osmotic concentration. The regulation of osmotic water permeability (Pf) in this terminal epithelial segment during ontogenetic differentiation has not been documented. The inner medullary collecting duct (IMCD), the terminal 40% of total segmental length, was dissected at two stages of postnatal ontogenetic differentiation from immature (days 7-15) and from mature (days 33-37) rat kidneys and perfused in vitro. Pf (micron/s) was measured (bath hyperosmotic) in the absence and presence of arginine vasopressin (AVP, 230 pM). Basal Pf was 32.3 +/- 4.03 (n = 26) in the immature IMCD (IMCDi) and 111.5 +/- 20.6 (n = 15) in the mature segment (IMCDm). AVP increased Pf in IMCDi from 46.4 +/- 10.5 to 102 +/- 25.7 micron/s, whereas in IMCDm the AVP-dependent change of Pf was from 104.2 +/- 41.2 to 693 +/- 176 micron/s. AVP (2,300 pM) did not further increase Pf in IMCDi. Forskolin (50 microM) changed Pf in IMCDi from 34.9 +/- 6.3 to 104.1 +/- 16 micron/s; the corresponding change in IMCDm was from 150 +/- 32 to 985.8 +/- 133 micron/s. An analogue of adenosine 3',5'-cyclic monophosphate (cAMP; 10(-3) M) increased Pf in IMCDi from 35.5 +/- 11.4 to 138.5 +/- 32.6 and in IMCDm from 79.6 +/- 32.3 to 702.2 +/- 283 micron/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Water permeability of apical and basolateral cell membranes of rat inner medullary collecting duct

1990 ◽  
Vol 259 (6) ◽  
pp. F986-F999 ◽  
Author(s):  
B. Flamion ◽  
K. R. Spring
Keyword(s):  
Water Flow ◽  
Water Permeability ◽  
Cell Membranes ◽  
Apical Membrane ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Volume Regulatory Decrease ◽  
Water Permeation ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct

To quantify the pathways for water permeation through the kidney medulla, knowledge of the water permeability (Posmol) of individual cell membranes in inner medullary collecting duct (IMCD) is required. Therefore IMCD segments from the inner two thirds of inner medulla of Sprague-Dawley rats were perfused in vitro using a setup devised for rapid bath and luminal fluid exchanges (half time, t1/2, of 55 and 41 ms). Differential interference contrast microscopy, coupled to video recording, was used to measure volume and approximate surface areas of single cells. Volume and volume-to-surface area ratio of IMCD cells were strongly correlated with their position along the inner medullary axis. Transmembrane water flow (Jv) was measured in response to a variety of osmotic gradients (delta II) presented on either basolateral or luminal side of the cells. The linear relation between Jv and delta II yielded the cell membrane Posmol, which was then corrected for membrane infoldings. Basolateral membrane Posmol was 126 +/- 3 microns/s. Apical membrane Posmol rose from a basal value of 26 +/- 3 microns/s to 99 +/- 5 microns/s in presence of antidiuretic hormone (ADH). Because of amplification of basolateral membrane, the ADH-stimulated apical membrane remained rate-limiting for transcellular osmotic water flow, and the IMCD cell did not swell significantly. Calculated transcellular Posmol, expressed in terms of smooth luminal surface, was 64 microns/s without ADH and 207 microns/s with ADH. IMCD cells in anisosmotic media displayed almost complete volume regulatory decrease but only partial volume regulatory increase.

scholarly journals Aldosterone Decreases Vasopressin-Stimulated Water Reabsorption in Rat Inner Medullary Collecting Ducts

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 967 ◽  
Author(s):  
Yanhua Wang ◽  
Fuying Ma ◽  
Eva L. Rodriguez ◽  
Janet D. Klein ◽  
Jeff M. Sands
Keyword(s):  
Direct Effect ◽  
Gene Transcription ◽  
Water Permeability ◽  
Collecting Duct ◽  
Osmotic Water Permeability ◽  
Water Reabsorption ◽  
Inner Medullary Collecting Duct ◽  
Urea Permeability ◽  
Osmotic Water ◽  
Medullary Collecting Duct

Aldosterone indirectly regulates water reabsorption in the distal tubule by regulating sodium reabsorption. However, the direct effect of aldosterone on vasopressin-regulated water and urea permeability in the rat inner medullary collecting duct (IMCD) has not been tested. We investigated whether aldosterone regulates osmotic water permeability in isolated perfused rat IMCDs. Adding aldosterone (500 nM) to the bath significantly decreased osmotic water permeability in the presence of vasopressin (50 pM) in both male and female rat IMCDs. Aldosterone significantly decreased aquaporin-2 (AQP2) phosphorylation at S256 but did not change it at S261. Previous studies show that aldosterone can act both genomically and non-genomically. We tested the mechanism by which aldosterone attenuates osmotic water permeability. Blockade of gene transcription with actinomycin D did not reverse aldosterone-attenuated osmotic water permeability. In addition to AQP2, the urea transporter UT-A1 contributes to vasopressin-regulated urine concentrating ability. We tested aldosterone-regulated urea permeability in vasopressin-treated IMCDs. Blockade of gene transcription did not reverse aldosterone-attenuated urea permeability. In conclusion, aldosterone directly regulates water reabsorption through a non-genomic mechanism. Aldosterone-attenuated water reabsorption may be related to decreased trafficking of AQP2 to the plasma membrane. There may be a sex difference apparent in the inhibitory effect of aldosterone on water reabsorption in the inner medullary collecting duct. This study is the first to show a direct effect of aldosterone to inhibit vasopressin-stimulated osmotic water permeability and urea permeability in perfused rat IMCDs.

Endothelin-1 inhibits AVP-stimulated osmotic water permeability in rat inner medullary collecting duct

1991 ◽  
Vol 261 (6) ◽  
pp. F951-F956 ◽  
Author(s):  
R. Oishi ◽  
H. Nonoguchi ◽  
K. Tomita ◽  
F. Marumo
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Renal Plasma Flow ◽  
Inhibitory Effect ◽  
Osmotic Water Permeability ◽  
Camp Generation ◽  
Osmotic Water ◽  
Collecting Ducts ◽  
Medullary Collecting Duct

Endothelin causes diuresis despite an accompanying decrease in glomerular filtration rate and renal plasma flow. Binding sites for endothelin are located not only in glomeruli but also in the inner medulla, possibly in inner medullary collecting ducts (IMCD). To determine whether endothelin has a direct tubular effect, effects of endothelin on water and urea transport were investigated using isolated microperfusion of rat IMCD segments in vitro. Endothelin, at 10(-10) and 10(-8) M, reversibly inhibited 10(-11) M arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf) by 18 and 24%, respectively. Endothelin (10(-8) M) also inhibited Pf by 23% in the presence of a much higher dose of AVP (10(-9) M), whereas endothelin had no effect on Pf in the absence of AVP. On the other hand, 10(-8) M endothelin did not inhibit Pf stimulated by 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). Endothelin had no inhibitory effect on AVP-stimulated urea permeability. These data suggest that endothelin can cause diuresis by inhibiting AVP-stimulated Pf in IMCD and that the site of action is previous to cAMP generation.

Characterization of apical and basolateral membrane conductances of rat inner medullary collecting duct

1989 ◽  
Vol 256 (5) ◽  
pp. F862-F868 ◽  
Author(s):  
B. A. Stanton
Keyword(s):  
Apical Membrane ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Passive Movement ◽  
Disulfonic Acid ◽  
Electrophysiological Properties ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct ◽  
K Concentration

Initial segments of the inner medullary collecting duct of the rat were perfused in vitro, and the electrophysiological properties of the apical and basolateral membranes were examined with KCl-filled microelectrodes. The fractional resistance of the apical membrane (FRa = Ra/Ra + Rbl) and the transepithelial resistance (RT) were estimated by cable analysis. In control tubules the transepithelial voltage (VT) averaged -2.2 mV, and the voltage across the basolateral membrane (Vbl) averaged -51.1 mV. RT was 11.9 k omega.cm (72.8 omega.cm2), and FRa was 0.94. Pretreatment of the rats with deoxycorticosterone (DOC)-pivalate for 7-10 days did not alter these electrophysiological properties. In control tubules, amiloride in the lumen (10(-5) M) changed VT from -3.0 to +1.4 mV and increased Vbl from -49.4 to -53.8 mV, RT from 12.5 to 13.6 k omega.cm, and FRa from 0.92 to 0.98. Thus the apical membrane is conductive to Na+. An increase of the bath K+ concentration from 4 to 15 mM caused an 18.8 mV depolarization of Vbl: barium in the bath also depolarized Vbl. A fivefold decrease in the [HCO3-] in the bath depolarized Vbl by 13.1 mV. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) blocked this depolarization. Thus the basolateral membrane is conductive to K+ and HCO3-. Experiments with ouabain revealed a Na+-K+-ATPase in the basolateral membrane. Taken together, the results support a model in which electrogenic Na+ absorption is driven by the Na+-K+-ATPase in the basolateral membrane, with passive movement of Na+ occurring through an amiloride-sensitive conductive pathway in the apical membrane.

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.

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.

Epac-mediated Ca2+ mobilization and exocytosis in inner medullary collecting duct

2006 ◽  
Vol 291 (4) ◽  
pp. F882-F890 ◽  
Author(s):  
Kay-Pong Yip
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Competitive Antagonist ◽  
Inner Medullary Collecting Duct ◽  
Camp Analog ◽  
Osmotic Water ◽  
Confocal Fluorescence ◽  
Intracellular Ca ◽  
Medullary Collecting Duct

PKA has traditionally been thought as the binding protein of cAMP for mediating arginine vasopressin (AVP)-regulated osmotic water permeability in kidney collecting duct. It is now known that cAMP also exerts its effects via Epac (exchange protein directly activated by cAMP) and that intracellular Ca2+ mobilization is necessary for AVP-induced apical exocytosis in inner medullary collecting duct (IMCD). The role of Epac as an effector of cAMP action in addition to PKA was investigated using confocal fluorescence microscopy in perfused IMCD. PKA inhibitors (1 μM H-89 or 10 μM KT-5720) at concentrations known to inhibit aquaporin-2 (AQP2) phosphorylation did not prevent AVP-induced Ca2+ mobilization and oscillations. Epac-selective cAMP agonist (8-pCPT-2′- O-Me-cAMP) mimicked AVP in triggering Ca2+ mobilization and oscillations, which was blocked by ryanodine but not by Rp-cAMP (a competitive antagonist of cAMP binding to PKA). 8-pCPT-2′- O-Me-cAMP also triggered apical exocytosis in the presence of a PKA inhibitor. Immunolocalization of AQP2 in perfused IMCD demonstrated that 8-pCPT-2′- O-Me-cAMP induces apical targeting of AQP2 and that AQP2 is abundant in junctional regions of basolateral membrane. Immunofluorescence study also confirmed the presence of Epac (isoform I) in IMCD. These results indicate that activation of Epac by an exogenous cAMP analog triggers intracellular Ca2+ mobilization and apical exocytotic insertion of AQP2 in IMCD.

Effects of ET-1 on water and chloride transport in cortical collecting ducts of the rat

1993 ◽  
Vol 264 (4) ◽  
pp. F690-F696 ◽  
Author(s):  
K. Tomita ◽  
H. Nonoguchi ◽  
Y. Terada ◽  
F. Marumo
Keyword(s):  
Water Permeability ◽  
Continuous Flow ◽  
Chloride Transport ◽  
Collecting Duct ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Osmotic Water ◽  
Collecting Ducts ◽  
Medullary Collecting Duct

Endothelin-1 (ET-1) is known as a vasoconstrictor peptide. However, recent reports suggested the effects on the transport of renal tubule. We previously reported that ET-1 inhibited arginine vasopressin (AVP)-dependent adenosine 3',5'-cyclic monophosphate in rat collecting ducts. Physiologically, ET-1 reversibly and significantly inhibited AVP-stimulated water permeability in inner medullary collecting duct (IMCD). We therefore investigated the effects on water and electrolyte transport in rat cortical collecting ducts (CCD), where Na and Cl are actively reabsorbed more than in IMCD. Pathogen-free male Sprague-Dawley rats weighing 80-120 g were used after treatment with deoxycorticosterone pivalate for 1-2 wk. Isolated CCD were microperfused in vitro. The Cl concentration was measured by a continuous-flow ultra-microcolorimeter, and the raffinose concentration was measured as a volume marker by a continuous-flow ultra-microfluorometer. In the presence of 10(-9) M AVP, 10(-8) M ET-1 significantly inhibited fluid absorption (nl.mm-1 x min-1) from 0.25 +/- 0.02 to 0.15 +/- 0.05 (mean +/- SE, n = 6, P < 0.01), Cl absorption (pmol.mm-1 x min-1) from 30. 6 +/- 2.8 to 14.9 +/- 4.0 (P < 0.01), and potential difference (mV) from -5.4 +/- 1.3 to -4.0 +/- 1.2 (P < 0.01). Similar results were obtained in the lower concentration of 10(-10) M AVP and 10(-10) M ET-1. As for the osmotic water permeability (microns/s), 10(-8) M ET-1 significantly inhibited this from 320.1 +/- 50.9 to 202.1 +/- 42.2 (n = 7, P < 0.01) in the presence of 10(-9) M AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

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