Developmental Changes in Proximal Tubule Tight Junction Proteins

Haddad, Maha; Lin, Fangming; Dwarakanath, Vangipuram; Cordes, Kimberly R.; Baum, Michel

doi:10.1203/01.pdr.0000151354.07752.9b

Cited by 13 publications

(6 citation statements)

References 45 publications

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“…LTA binds to specific glycoproteins present only in proximal tubule brush border (apical) membranes. 35,36 We demonstrate that AM fractions isolated with LTA were enriched with villin, validating the isolation of the outer brush border membrane fraction. Our results show that intrarenal administration of fenoldopam increased the quantity of AT 2 R protein in these AMs.…”

Section: Salomone Et Al D 1 and At 2 Receptor Interactions In Natriursupporting

confidence: 67%

Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

et al. 2007

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Abstract-We explored the effects of direct renal interstitial stimulation of dopamine D 1 -like receptors with fenoldopam, a selective D 1 -like receptor agonist, on renal sodium excretion and angiotensin type-2 (AT 2 ) receptor expression and cellular distribution in rats on a high-sodium intake. In contrast to vehicle-infused rats, sodium excretion increased in fenoldopam-infused rats during each of three 1-hour experimental periods (Ͻ0.001 Key Words: angiotensin Ⅲ dopamine Ⅲ receptors Ⅲ sodium excretion Ⅲ natriuresis Ⅲ receptor trafficking Ⅲ kidney T he kidney is endowed with 2 local hormonal systems that play a major role in the regulation of sodium (Na ϩ ) transport across the renal proximal tubule (RPT): the reninangiotensin system and the dopaminergic system. In vitro studies show that angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system, acts at angiotensin type-1 (AT 1 ) receptors on RPT cell membranes to increase Na ϩ transport across the cell from the lumen into the interstitial space and peritubular capillaries by stimulating Na ϩ -hydrogen (H ϩ ) exchanger-3 (NHE-3) and Na ϩ ,K ϩ -ATPase activities, respectively. 1 On the other hand, dopamine (DA), synthesized in and secreted from RPT cells, activates D 1 -like receptors (D 1 and D 5 receptor subtypes) on RPT cells to inhibit Na ϩ reabsorption by inhibiting NHE-3 and Na ϩ ,K ϩ -ATPase activities. 2,3 Although these 2 hormonal systems act in opposite directions on RPT Na ϩ transport in vitro, little is known regarding the physiological interactions of intrarenal Ang II and DA in the control of Na ϩ excretion in vivo. Approximately 50% of basal Na ϩ excretion is mediated by the paracrine action of renal DA on RPT D 1 -like receptors. 4,5 However, the mechanisms of receptor interaction that govern DA-induced natriuresis are incompletely understood. DA downregulates AT 1 receptors (AT 1 Rs) in the RPT. 6 However, Ang II binds to angiotensin type-2 (AT 2 ) receptors (AT 2 Rs), as well as AT 1 Rs, and the effects of DA on AT 2 Rs are unknown.AT 2 Rs are expressed in the RPT but have a low degree of renal expression compared with that of AT 1 Rs. 7 The present study explores the direct renal interstitial (RI) stimulation of D 1 receptors with fenoldopam, a selective D 1 -like receptor agonist, and its effects on renal Na ϩ excretion and AT 2 R expression in the rat. We demonstrate that natriuresis induced by stimulation of renal D 1 -like receptors requires AT 2 R expression and recruitment to the RPT plasma membrane. In the presence of AT 2 R inhibition, D 1 -like receptor stimulation is not able to induce renal Na ϩ excretion.

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Section: Salomone Et Al D 1 and At 2 Receptor Interactions In Natriursupporting

confidence: 67%

Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

et al. 2007

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“…Claudin 2 is a cation-selective claudin (30), which may account for the higher P Na /P Cl measured in the PCT of neonates. Occludin, on the other had, has a fourfold greater expression in adult tubules than in neonate tubules (16). As speculation, it is possible that changes in claudin 2, occludin, or other proximal tubule tight junction proteins may account for the changes in paracellular properties found in this study.…”

Section: Discussionmentioning

confidence: 57%

“…Claudin 2 and occludin have been identified as tight junction proteins in the proximal tubule (11,13,21,25). Using immunoblot and immunohistochemistry, we have found in the rat that claudin 2 has a fourfold greater abundance in neonate proximal tubules than in adult tubules (16). Claudin 2 is a cation-selective claudin (30), which may account for the higher P Na /P Cl measured in the PCT of neonates.…”

Section: Discussionmentioning

confidence: 82%

Maturation of rat proximal tubule chloride permeability

Baum¹,

Quigley²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 Ϯ 1.3 ϫ 10 Ϫ5 cm/s in neonate rat proximal convoluted tubule and 16.1 Ϯ 2.3 ϫ 10 Ϫ5 cm/s in adult rat proximal convoluted tubule (P Ͻ 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 Ϯ 0.6 ϫ 10 Ϫ5 cm/s vs. 9.3 Ϯ 0.6 ϫ 10 Ϫ5 cm/s, P Ͻ 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities (P HCO3/PCl) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability (PNa/PCl) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule PNa/ P Cl with postnatal development (1.31 Ϯ 0.12 in neonates vs. 0.75 Ϯ 0.06 in adults, P Ͻ 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 Ϯ 0.8 vs. 4.6 Ϯ 0.1 ⍀ ⅐ cm 2 , P Ͻ 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development. paracellular pathway; mannitol permeability THE ADULT PROXIMAL TUBULE reabsorbs over half of the filtered chloride (2,5,6,18,27,28). Active transcellular chloride is via the parallel operation of the Na ϩ /H ϩ exchanger and a Cl/base exchanger (5, 27). The other half of chloride transport by the proximal tubule is passive, paracellular, and in large part, dependent on the chloride permeability. Thus the characteristics of the paracellular pathway can have a substantive effect on NaCl transport by the proximal tubule.Previous studies examining the maturational changes in paracellular permeability have been conflicting. In a study (17) where solutes were injected into the early proximal tubule of guinea pigs and the urine was collected from the ipsilateral kidney, recovery of sucrose and creatinine did not vary with age and were comparable to inulin. However, mannitol recovery increased from 92% at 1 day of age to 100% at 49 days of age (17). Whereas these studies were indirect and assessed mannitol absorption, a sugar that is not actively transported along the entire nephron, these data were consistent with a more permeable paracellular pathway in neonates than in adults.We have examined the permeability properties of the rabbit proximal tubule (23, 29). We found that the neonate had lower proximal tubule chloride permeability, but there was no maturational difference in th...

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“…We have previously shown that claudin 2 protein expression is fourfold greater in neonatal proximal tubules than in adult proximal tubules while occludin protein abundance increases during postnatal development using immunoblot analysis and immunohistochemistry in the rat (18). Claudin 2 has been shown to increase the permeability of sodium, and the high paracellular sodium-to-chloride permeability in neonates compared with adults may be explained by the high level of expression of this claudin (50).…”

Section: Discussionmentioning

confidence: 96%

Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins

Abuazza¹,

Becker²,

Williams³

et al. 2006

American Journal of Physiology-Renal Physiology

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106

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The adult proximal tubule is a low-resistance epithelium where there are high rates of both active transcellular and passive paracellular NaCl transport. We have previously demonstrated that the neonatal rabbit and rat proximal tubule have substantively different passive paracellular transport properties than the adult proximal tubule, which results in a maturational change in the paracellular passive flux of ions. Neonatal proximal tubules have a higher PNa/PCl ratio and lower chloride and bicarbonate permeabilities than adult proximal tubules. Claudins are a large family of proteins which are the gate keepers of the paracellular pathway, and claudin isoform expression determines the permeability characteristics of the paracellular pathway. Previous studies have shown that claudins 1, 2, 3, 4, 5, 7, 8, 10, 11, 12, 15, and 16 are expressed in the adult mouse kidney. To determine whether there are developmental claudin isoforms, we compared the claudin isoforms present in the neonatal and adult kidney using RT-PCR to detect mRNA of claudin isoforms. Claudin 6, claudin 9, and claudin 13 were either not expressed or barely detectable in the adult mouse kidney using traditional PCR, but were expressed in the neonatal mouse kidney. Using real-time RT-PCR, we were able to detect a low level of claudin 6 mRNA expression in the adult kidney compared with the neonate, but claudin 9 and claudin 13 were only detected in the neonatal kidney. There was the same maturational decrease in these claudin proteins with Western blot analysis. Immunohistochemistry showed high levels of expression of claudin 6 in neonatal proximal tubules, thick ascending limb, distal convoluted tubules, and collecting ducts in a paracellular distribution but there was no expression of claudin 6 in the adult kidney. Using real-time RT-PCR claudin 6 and 9 mRNA were present in 1-day-old proximal convoluted tubules and were virtually undetectable in proximal convoluted tubules from adults. Claudin 13 was not detectable in neonatal or adult proximal convoluted tubules. In summary, we have identified developmentally expressed claudin isoforms, claudin 6, claudin 9, and claudin 13. These paracellular proteins may play a role in the maturational changes in paracellular permeability.

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Developmental Changes in Proximal Tubule Tight Junction Proteins

Cited by 13 publications

References 45 publications

Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Maturation of rat proximal tubule chloride permeability

Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins

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Developmental Changes in Proximal Tubule Tight Junction Proteins

Cited by 13 publications

References 45 publications

Intrarenal Dopamine D 1 -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Intrarenal Dopamine D 1 -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Maturation of rat proximal tubule chloride permeability

Claudins 6, 9, and 13 are developmentally expressed renal tight junction proteins

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Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism

Intrarenal Dopamine D ₁ -Like Receptor Stimulation Induces Natriuresis via an Angiotensin Type-2 Receptor Mechanism