ANG II reduces net acid secretion in rat outer medullary collecting duct

Wall, Susan M.; Fischer, Michael P.; Glapion, Dawn M.; Calzada, Mae De La

doi:10.1152/ajprenal.00400.2002

Cited by 18 publications

(17 citation statements)

References 41 publications

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“…ANG II also stimulates proton secretion by A-IC and induces apical V-ATPase accumulation in the CCD (47). However, while ANG II was reported to reduce proton secretion in the OMCD in one study (66), another showed a Ca 2ϩ -dependent increase in V-ATPase activity and trafficking in this segment upon ANG II stimulation (50). Finally, aldosterone also induces apical V-ATPase accumulation in IC from the OMCD in a PKC-dependent manner (68).…”

Section: Discussionmentioning

confidence: 97%

“…In contrast, sAC may be an important regulator of the V-ATPase when excessive HCO 3 Ϫ is delivered distally due to deficient reabsorption in the proximal tubule. This could occur during dysfunctional states such as Fanconi syndrome, after treatment with the carbonic anhydrase inhibitor acetazolamide, or following supplementation with NaHCO 3 Ϫ as discussed, for example, by Wall et al (66).…”

Section: Discussionmentioning

confidence: 99%

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cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

Păunescu

Ljubojević

Russo

et al. 2010

American Journal of Physiology-Renal Physiology

106

109

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We show here that the cell-permeant cAMP analog CPT-cAMP, infused in vivo, results in an almost twofold increase in apical V-ATPase accumulation in AE1-positive A-IC within 15 min and that these cells develop an extensive array of apical microvilli compared with controls. In contrast, no significant change in VATPase distribution could be detected by immunocytochemistry in B-intercalated cells at the acute time point examined. To show a direct effect of cAMP on A-IC, we prepared cell suspensions from the medulla of transgenic mice expressing EGFP in IC (driven by the B1-subunit promoter of the V-ATPase) and exposed them to cAMP analogs in vitro. Three-dimensional reconstructions of confocal images revealed that cAMP induced a time-dependent growth of apical microvilli, starting within minutes after addition. This effect was blocked by the PKA inhibitor myristoylated PKI. These morphological changes were paralleled by increased cAMP-mediated proton extrusion (pHi recovery) by A-IC in outer medullary collecting ducts measured using the ratiometric probe BCECF. These results, and our prior data showing that the bicarbonate-stimulated soluble adenylyl cyclase (sAC) is highly expressed in kidney intercalated cells, support the idea that cAMP generated either by sAC, or by activation of other signaling pathways, is part of the signal transduction mechanism involved in acid-base sensing and V-ATPase membrane trafficking in kidney intercalated cells. proton pump; H ϩ -ATPase; immunocytochemistry; membrane trafficking; acid-base sensing; phosphorylation PROTON SECRETION BY THE RENAL proximal tubule and collecting duct is induced by a variety of factors, including systemic acidemia and basolateral CO 2 elevation. This increased acid secretion occurs at least in part by inducing the apical accumulation of the vacuolar proton pumping ATPase (V-ATPase) in A-type intercalated cells (A-IC) in both the cortical and medullary collecting ducts of the kidney. Simultaneously, bicarbonate-secreting B-type IC (B-IC) are "inactivated" by acidosis, a process that involves the endocytotic removal of basolateral plasma membrane V-ATPases that are characteristic of this cell type (6, 53). The sensing mechanism in IC that detects changes in acid-base status and regulates plasma membrane V-ATPase expression remains largely unknown.Based on our work on proton-secreting cells in the epididymis, we proposed that luminal bicarbonate may play a central role in this process via its stimulatory effect on the soluble adenylyl cyclase (sAC), an atypical cyclase distinct from canonical transmembrane adenylyl cyclases, which generates intracellular cAMP in response to increased intracellular HCO 3 Ϫ concentration (42). We have previously shown that sAC is expressed in many segments of the kidney tubule, but its expression is especially elevated in IC, where it is colocalized in a protein complex with the V-ATPase. Furthermore, sAC and V-ATPase are concentrated together in the apical domain of IC of rats treated with the carbonic anhydrase inhibitor ac...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

Păunescu

Ljubojević

Russo

et al. 2010

American Journal of Physiology-Renal Physiology

106

109

View full text Add to dashboard Cite

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“…Despite a dramatic up-regulation of H ϩ secretion in the proximal and distal tubules by Ang II, infusion of Ang II does not produce a metabolic alkalosis, suggesting a compensatory regulation of acid secretion in other segments of the nephron. To support this notion, Ang II decreased H ϩ secretion in the perfused rat outer medullary collecting ducts (Weiner et al, 1995;Wall et al, 2003). This can be explained by a reduction in H ϩ -ATPase activity (Tojo et al, 1994;Valles and Manucha, 2000).…”

Section: B Role Of Angiotensin II In the Regulation Of Tubular Functionmentioning

confidence: 90%

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Kobori

Nangaku

Navar

et al. 2007

Pharmacological Reviews

1,105

1,219

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“…15 Moreover, decreased H ϩ secretion was found in perfused medullary thick ascending limb and outer medullary collecting duct segments exposed to Ang II. 38,39 Aldosterone increases H ϩ secretion, directly in the outer medullary collecting duct and indirectly via voltage effects secondary to increased sodium reabsorption in chargecoupled device segment. 10,40 Our findings in ADX rats suggest that the removal of aldosterone results in a decrease in the relative abundance and expression of B1 H ϩ -ATPase in the medullary but not the cortical collecting tubule.…”

Section: Valles Et Al H ؉ -Atpase Expression In Collecting Ductsmentioning

confidence: 99%

Angiotensin II Increases H ⁺ -ATPase B1 Subunit Expression in Medullary Collecting Ducts

et al. 2005

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Abstract-Metabolic alkalosis is a common feature of hypokalemic hypertensive syndromes associated with angiotensin II excess. The alkalosis-generating effect of angiotensin II is usually ascribed to its stimulatory effect on aldosterone secretion, a hormone that upregulates collecting duct hydrogen ion secretion. We studied the effect of angiotensin II infusions on the expression of B1 and a4 protein, subunits of the renal H ϩ -ATPase in adrenalectomized rats. Adrenalectomized rats were given either angiotensin II or vehicle for 7 days via osmotic mini-pumps. H ϩ -ATPase B1 protein expression was evaluated by Western blot analysis in isolated medulla and cortex plasma membrane preparations from one kidney, whereas the contralateral kidney was used for immunostaining. By Western blotting, the relative abundance of B1 protein was 2-fold higher in renal medulla membranes from rats with intact adrenal glands (sham surgery) than from adrenalectomized rats (219Ϯ47%, nϭ12; PϽ0.05). In contrast to renal medulla, adrenalectomy did not significantly alter the relative abundance of B1 protein in renal cortex. Angiotensin II also did not significantly alter the relative levels of B1 protein in the cortex, but it increased it significantly in renal medullary membranes (231Ϯ56%, nϭ8; PϽ0.005). Moreover, enhanced H ϩ -ATPase B1 subunit protein immunoreactivity was found in medullary collecting duct segments of rats infused with angiotensin II. In contrast to B1, expression of a4, another subunit of the H ϩ -ATPase was not altered by adrenalectomy or angiotensin II. We conclude that adrenalectomy decreases whereas angiotensin II increases H ϩ -ATPase B1 subunit expression in medullary, but not in cortical collecting ducts. By increasing the relative abundance of the B1 subunit of H ϩ -ATPase in the collecting duct, angiotensin II excess may lead to increased hydrogen ion secretion and thus metabolic alkalosis-a common feature of hypertensive syndromes associated with angiotensin II overactivity.

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ANG II reduces net acid secretion in rat outer medullary collecting duct

Cited by 18 publications

References 41 publications

cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Angiotensin II Increases H ⁺ -ATPase B1 Subunit Expression in Medullary Collecting Ducts

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ANG II reduces net acid secretion in rat outer medullary collecting duct

Cited by 18 publications

References 41 publications

cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Angiotensin II Increases H + -ATPase B1 Subunit Expression in Medullary Collecting Ducts

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Angiotensin II Increases H ⁺ -ATPase B1 Subunit Expression in Medullary Collecting Ducts