PMID- 11181405
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20171213
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 280
IP  - 3
DP  - 2001 Mar
TI  - Remodeling the cellular profile of collecting ducts by chronic carbonic anhydrase 
      inhibition.
PG  - F437-48
AB  - Factors regulating the differentiated phenotype of principal cells (PC) and A- 
      and B-intercalated cells (IC) in kidney collecting ducts are poorly understood. 
      However, we have shown previously that carbonic anhydrase II (CAII)-deficient 
      mice have no IC in their medullary collecting ducts, suggesting a potential role 
      for this enzyme in determining the cellular composition of this tubule segment. 
      We now report that the cellular profile of the collecting ducts of adult rats can 
      be remodeled by inhibiting CA activity in rats by using osmotic pumps containing 
      acetazolamide. The 31-kDa subunit of the vacuolar H(+)-ATPase, the 
      sodium/hydrogen exchanger regulatory factor NHE-RF, and the anion exchanger AE1 
      were used to identify IC subtypes by immunofluorescence staining, while aquaporin 
      2 and aquaporin 4 were used to identify PC. In the cortical collecting ducts of 
      animals treated with acetazolamide for 2 wk, the percentage of B-IC decreased 
      significantly (18 +/- 2 vs. 36 +/- 4%, P < 0.01) whereas the percentage of A-IC 
      increased (82 +/- 2 vs. 64 +/- 4%, P < 0.01) with no change in the percentage of 
      total IC in the epithelium. In some treated rats, B-IC were virtually 
      undetectable. In the inner stripe of the outer medulla, the percentage of IC 
      increased in treated animals (48 +/- 2 vs. 37 +/- 3%, P < 0.05) and the 
      percentage of PC decreased (52 +/- 2 vs. 63 +/- 3%, P < 0.05). Moreover, IC 
      appeared bulkier, protruded into the lumen, and showed a significant increase in 
      the length of their apical (20.8 +/- 0.5 vs. 14.6 +/- 0.4 microm, P < 0.05) and 
      basolateral membranes (25.8 +/- 0.4 vs. 23.8 +/- 0.5 microm, P < 0.05) compared 
      with control rats. In the inner medullary collecting ducts of treated animals, 
      the number of IC in the proximal third of the papilla was reduced compared with 
      controls (11 +/- 4 vs. 40 +/- 11 IC/mm(2), P < 0.05). These data suggest that CA 
      activity plays an important role in determining the differentiated phenotype of 
      medullary collecting duct epithelial cells and that the cellular profile of 
      collecting ducts can be remodeled even in adult rats. The relative depletion of 
      cortical B-IC and the relative increase in number and hyperplasia of A-IC in the 
      medulla may be adaptive processes that would tend to correct or stabilize the 
      metabolic acidosis that would otherwise ensue following systemic carbonic 
      anhydrase inhibition.
FAU - Bagnis, C
AU  - Bagnis C
AD  - Program in Membrane Biology, Massachusetts General Hospital, Boston, 
      Massachusetts 02120, USA. bagnis@receptor.mgh.harvard.edu
FAU - Marshansky, V
AU  - Marshansky V
FAU - Breton, S
AU  - Breton S
FAU - Brown, D
AU  - Brown D
LA  - eng
GR  - DK-38452/DK/NIDDK NIH HHS/United States
GR  - DK-42956/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
RN  - O3FX965V0I (Acetazolamide)
SB  - IM
MH  - Acetazolamide/administration & dosage/*pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Carbonic Anhydrase Inhibitors/administration & dosage/*pharmacology
MH  - Carbonic Anhydrases/physiology
MH  - Diuresis/drug effects
MH  - Infusion Pumps
MH  - Kidney Medulla/cytology
MH  - Kidney Tubules, Collecting/cytology/*drug effects/*physiology/ultrastructure
MH  - Microscopy, Electron
MH  - Natriuresis/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Values
MH  - Time Factors
EDAT- 2001/02/22 11:00
MHDA- 2001/03/27 10:01
CRDT- 2001/02/22 11:00
PHST- 2001/02/22 11:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/02/22 11:00 [entrez]
AID - 10.1152/ajprenal.2001.280.3.F437 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2001 Mar;280(3):F437-48. doi: 
      10.1152/ajprenal.2001.280.3.F437.