Influence of chronic ADH treatment on adenylate cyclase and ATPase activity in distal nephron segments of diabetes insipidus Brattleboro rats

1985 ◽  
Vol 405 (3) ◽  
pp. 216-222 ◽  
Author(s):  
M. M. Trinh-Trang-Tan ◽  
L. Bankir ◽  
A. Doucet ◽  
G. El Mernissi ◽  
M. Imbert-Teboul ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Atpase Activity ◽  
Diabetes Insipidus ◽  
Brattleboro Rats ◽  
Distal Nephron ◽  
Nephron Segments

Changes in tubular basolateral membrane markers after chronic DOCA treatment

1983 ◽  
Vol 245 (1) ◽  
pp. F100-F109 ◽  
Author(s):  
G. El Mernissi ◽  
D. Chabardes ◽  
A. Doucet ◽  
A. Hus-Citharel ◽  
M. Imbert-Teboul ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Atpase Activity ◽  
Protein Content ◽  
Basolateral Membrane ◽  
Chronic Administration ◽  
Distal Nephron ◽  
Nephron Segments ◽  
Collecting Tubule ◽  
Nephron Segment ◽  
Cortical Collecting Tubule

Chronic administration of DOCA to rabbits is known to increase the surface area of the basolateral membrane and the Na-K-ATPase activity of the cortical collecting tubule (CCT). We attempted to ascertain 1) whether Na-K-ATPase is the only basolateral membrane marker induced by DOCA, and 2) whether CCT is the only nephron segment affected by this steroid. We measured the activity of Na-K-ATPase and adenylate cyclase (AC) and the protein content of nephron segments microdissected from control and DOCA-treated rabbits. Morphogenic effects of DOCA, assessed by 30-60% increases in protein content, were specifically observed in the distal convoluted tubule, CCT, and medullary collecting tubule. When expressed as a function of tubular length, Na-K-ATPase activity rose from 80 to 200% in all these segments, whereas the increments in AC of 40-70%, observed in response to four different hormones, occurred only in some of them. When expressed as a function of protein content, Na-K-ATPase activity increased but AC activity remained unchanged. This study indicates that the morphogenic action resulting from chronic DOCA administration affects the entire rabbit distal nephron. During this action Na-K-ATPase is the preferentially induced enzyme.

Impaired Response to Vasopressin of Adenylate Cyclase of the Thick Ascending Limb of Henle’s Loop in Brattleboro Rats with Diabetes insipidus

1978 ◽  
Vol 1 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Martine Imbert-Teboul ◽  
Danielle Chabardès ◽  
Madeleine Montégut ◽  
André Clique ◽  
François Morel
Keyword(s):  
Adenylate Cyclase ◽  
Diabetes Insipidus ◽  
Thick Ascending Limb ◽  
Brattleboro Rats

Effects of PTH, calcitonin, and cAMP on calcium transport in rabbit distal nephron segments

1990 ◽  
Vol 259 (3) ◽  
pp. F408-F414 ◽  
Author(s):  
T. Shimizu ◽  
K. Yoshitomi ◽  
M. Nakamura ◽  
M. Imai
Keyword(s):  
Parathyroid Hormone ◽  
Adenylate Cyclase ◽  
Calcium Transport ◽  
Collecting Duct ◽  
Exchange Process ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Nephron Segments ◽  
Bathing Fluid

Distal nephron segments are heterogenous with respect to adenylate cyclase responses to stimulation with parathyroid hormone (PTH) or calcitonin (CT). We examined effects of these hormones and of 8-(p-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPTcAMP) on net Ca absorption (Jnet Ca2+, pmol.min-1.mm-1) in rabbit distal nephron segments by in vitro microperfusion technique. We studied three segments, including distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). PTH (1 nM) in bath significantly increased Jnet Ca2+ from 2.28 +/- 0.35 to 9.44 +/- 1.13 in CNT, but did not affect Jnet Ca2+ in DCT or CCD. CT (1 nM) in bath significantly increased Jnet Ca2+ from 1.58 +/- 0.29 to 4.45 +/- 1.01 in DCT, whereas it did not affect Jnet Ca2+ either in CNT or in CCD. CPTcAMP (30 microM) in bath significantly increased Jnet Ca2+ from 2.29 +/- 0.42 to 3.97 +/- 0.43 in DCT and from 2.43 +/- 0.18 to 5.83 +/- 0.37 in CNT, but it did not affect Jnet Ca2+ in CCD. When Na+ was removed from bathing fluid or when 0.1 mM ouabain was added to bath, Jnet Ca2+ in both DCT and CNT significantly decreased. Furthermore, stimulatory effects of PTH and CT on Ca2+ absorption in the respective segments were abolished under these conditions. These results suggest that PTH and CT increase Ca2+ absorption in CNT and DCT, respectively, through cAMP-mediated mechanisms. Presence of a basolateral Na(+)-Ca2+ exchange process seems to be a prerequisite for effects of these hormones. However, exact intracellular mechanisms remain uncertain.

Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion

1987 ◽  
Vol 253 (3) ◽  
pp. F418-F423 ◽  
Author(s):  
A. Doucet ◽  
S. Marsy
Keyword(s):  
Atpase Activity ◽  
Rat Kidney ◽  
Intercalated Cells ◽  
Distal Nephron ◽  
Morphological Alterations ◽  
Nephron Segments ◽  
Collecting Tubule ◽  
K Depletion ◽  
Cortical Collecting Tubule

Intercalated cells of the distal segments of the mammalian nephron are able to reabsorb K through an active mechanism, particularly during K depletion. However, the molecular basis of this transport is unknown. Therefore, we attempted to determine whether a K-ATPase similar to K-H-ATPase described in gastric mucosa and colon might be present in segments of the distal nephron and thereby account for active K reabsorption. K-stimulated ATPase activity was detected in microdissected segments of rabbit nephron: its activity was proportional to the density of intercalated cells, since it was highest in the connecting tubule, intermediate in the cortical collecting tubule, lowest in the outer medullary collecting tubule, and was not detectable in all other nephron segments. K-ATPase had a high affinity for K (Km approximately equal to 0.2-0.4 mM), was inhibited by vanadate and omeprazole, and was insensitive to ouabain, indicating that it is different from Na+-K+-ATPase but similar to K-H-ATPase. In the rat kidney, K-ATPase was also detected in the collecting tubule and its activity was markedly increased (+100-200%) following K depletion. This stimulation occurred before morphological alterations and might therefore be a primary event responsible for K conservation during K depletion. In summary, these results demonstrate the presence of a vanadate-sensitive, ouabain-insensitive K-ATPase activity in distal nephron segments of mammalian tubules. It is suggested that K-ATPase activity originates in intercalated cells where it might account, at least in part, for K reabsorption.

Antidiuretic antagonism and agonism of 1-deamino-pentamethylene-2-d-phenylalanine-4-isoleucine-arginine vasopressin in rats with diabetes insipidus

1987 ◽  
Vol 112 (3) ◽  
pp. 439-442 ◽  
Author(s):  
H. Vilhardt ◽  
S. Lundin
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Test Model ◽  
Brattleboro Rats ◽  
Experimental Conditions ◽  
Vasopressin Antagonist ◽  
Agonist Action

ABSTRACT Using implanted minipumps it was shown over a period of 7 days that the vasopressin antagonist, 1-deamino-pentamethylene-2-d-Phe-4-Ile-arginine vasopressin, caused increased diuresis in normal rats and reversed vasopressin- or oxytocin-induced antidiuresis in Brattleboro rats. When the antagonist was infused alone in Brattleboro rats it induced a marked antidiuretic response, indicating that the analogue also possessed agonistic properties. The agonist action could not be demonstrated in anaesthetized, hydrated normal rats. In these animals the analogue behaved as a pure antagonist. It is concluded that analogues which behave as antagonists in one test model may display agonistic properties under different experimental conditions. J. Endocr. (1987) 112, 439–442

scholarly journals Renal release of N-acetyl-seryl-aspartyl-lysyl-proline is part of an antifibrotic peptidergic system in the kidney

2019 ◽  
Vol 316 (1) ◽  
pp. F195-F203 ◽  
Author(s):  
Cesar A. Romero ◽  
Nitin Kumar ◽  
Pablo Nakagawa ◽  
Morel E. Worou ◽  
Tang-Dong Liao ◽  
...  
Keyword(s):  
De Novo ◽  
Renal Medulla ◽  
Distal Portion ◽  
Distal Nephron ◽  
Sprague Dawley ◽  
Nephron Segments ◽  
Long Term Effect ◽  
Chronic Infusion ◽  
A Minor ◽  
Stop Flow

The antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is released from thymosin-β4 (Tβ4) by the meprin-α and prolyl oligopeptidase (POP) enzymes and is hydrolyzed by angiotensin-converting enzyme (ACE). Ac-SDKP is present in urine; however, it is not clear whether de novo tubular release occurs or if glomerular filtration is the main source. We hypothesized that Ac-SDKP is released into the lumen of the nephrons and that it exerts an antifibrotic effect. We determined the presence of Tβ4, meprin-α, and POP in the kidneys of Sprague-Dawley rats. The stop-flow technique was used to evaluate Ac-SDKP formation in different nephron segments. Finally, we decreased Ac-SDKP formation by inhibiting the POP enzyme and evaluated the long-term effect in renal fibrosis. The Tβ4 precursor and the releasing enzymes meprin-α and POP were expressed in the kidneys. POP enzyme activity was almost double that in the renal medulla compared with the renal cortex. With the use of the stop-flow technique, we detected the highest Ac-SDKP concentrations in the distal nephron. The infusion of a POP inhibitor into the kidney decreased the amount of Ac-SDKP in distal nephron segments and in the proximal nephron to a minor extent. An ACE inhibitor increased the Ac-SDKP content in all nephron segments, but the increase was highest in the distal portion. The chronic infusion of a POP inhibitor increased kidney medullary fibrosis, which was prevented by Ac-SDKP. We conclude that Ac-SDKP is released by the nephron and is part of an important antifibrotic system in the kidney.

scholarly journals Proximal and Distal Nephron-specific Adaptation to Furosemide

2021 ◽  
Author(s):  
Aram J. Krauson ◽  
Steven Schaffert ◽  
Elisabeth M. Walczak ◽  
Jonathan M. Nizar ◽  
Gwen M. Holdgate ◽  
...  
Keyword(s):  
Cell Number ◽  
Differentially Expressed ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Distal Nephron ◽  
Transcriptional Responses ◽  
Cell Hyperplasia ◽  
Diuretic Resistance ◽  
Nephron Segments ◽  
Renal Tubular

ABSTRACTFurosemide, a widely prescribed diuretic for edema-forming states, inhibits sodium reabsorption in the thick ascending limb of the nephron. Tubular adaptation to diuretics has been observed, but the range of mechanisms along the nephron has not been fully explored. Using morphometry, we show that furosemide induces renal tubular epithelial hyperplasia selectively in distal nephron segments. By comparison, we find progressive cellular hypertrophy in proximal and distal nephron segments. We next utilize single cell RNA sequencing of vehicle- and furosemide-treated mice to define potential mechanisms of diuretic resistance. Consistent with distal tubular cell hyperplasia, we detect a net increase in DCT cell number and Birc5, an anti-apoptotic and pro-growth gene, in a subset of DCT cells, as the most prominently up-regulated gene across the nephron. We also map a gradient of cell-specific transcriptional changes congruent with enhanced distal sodium transport. Furosemide stimulates expression of the mitogen IGF-1. Thus, we developed a mouse model of inducible deletion of renal tubular IGF-1 receptor and show reduced kidney growth and proximal, but not distal, tubular hypertrophy by furosemide. Moreover, genes that promote enhanced bioavailability of IGF-1 including Igfbp1 and Igfbp5 are significantly and differentially expressed in proximal tubular segments and correspond to IGF-1R-dependent hypertrophy. In contrast, downstream PI3-kinase signaling genes including Pdk1, Akt1, Foxo3, FKBP4, Eif2BP4, and Spp1 are significantly and differentially expressed in distal nephron segments and correspond to IGF-1R-independent hypertrophy. These findings highlight novel mechanisms of tubular remodeling and diuretic resistance, provide a repository of transcriptional responses to a common drug, and expand the implications of long-term loop diuretic use for human disease.

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