Cellular localization, membrane distribution, and possible function of guanylyl cyclases A and 1 in collecting ducts of rat

Hirsch, Jochen R.

doi:10.1016/s0008-6363(00)00297-2

Cited by 16 publications

(17 citation statements)

References 46 publications

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“…Previous studies showed that GC-G mRNA is expressed in rat kidney, [12][13][14] and we found GC-G mRNA expressed in the mouse kidney by reverse transcriptase-PCR (RT-PCR) analysis with three independent pairs of mouse GC-G-specific oligonucleotide primers ( Figure 1A). To verify further the cell type expression of GC-G, we performed immunohistochemistry using an anti-GC-G-specific antibody in mouse kidney sections.…”

Section: Renal Expression Of Gc-g Under Normal and I/r Conditionsmentioning

confidence: 64%

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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The membrane forms of guanylyl cyclase (GC) serve as cell-surface receptors that synthesize the second messenger cGMP, which mediates diverse cellular processes. Rat kidney contains mRNA for the GC-G isoform, but the role of this receptor in health and disease has not been characterized. It was found that mouse kidney also contains GC-G mRNA, and immunohistochemistry identified GC-G protein in the epithelial cells of the proximal tubule and collecting ducts. Six hours after ischemia-reperfusion (I/R) injury, GC-G mRNA and protein expression increased three-fold and remained upregulated at 24 h. For determination of whether GC-G mediates I/R injury, a mutant mouse with a targeted disruption of the GC-G gene (Gucy2g) was created. At baseline, no histologic abnormalities were observed in GC-G Ϫ/Ϫ mice. After I/R injury, elevations in serum creatinine and urea were attenuated in GC-G Ϫ/Ϫ mice compared with wild-type controls, and this correlated with less tubular disruption, less tubular cell apoptosis, and less caspase-3 activation. Measures of inflammation (number of infiltrating neutrophils, myeloperoxidase activity, and induction of IL-6 and P-selectin) and activation of NF-B were lower in GC-G Ϫ/Ϫ mice compared with wild-type mice. Direct transfer of a GC-G expression plasmid to the kidneys of GC-G Ϫ/Ϫ mice resulted in a dramatically higher mortality after renal I/R injury, further supporting a role for GC-G in mediating injury. In summary, GC-G may act as an early signaling molecule that promotes apoptotic and inflammatory responses in I/R-induced acute renal injury.

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Section: Renal Expression Of Gc-g Under Normal and I/r Conditionsmentioning

confidence: 64%

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Lin

Cheng²,

Hou

et al. 2008

Journal of the American Society of Nephrology

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“…The minor variation in the expression pattern observed between rat and mouse is not surprising because species-specific differences occur quite frequently. Even expression differences in the kidney between two strains of the same species are known [54].…”

Section: Discussionmentioning

confidence: 99%

Cellular Localization of THIK-1 (K2P13.1) and THIK-2 (K2P12.1) K+ Channels in the Mammalian Kidney

Theilig¹,

Goranova²,

Hirsch

et al. 2008

Cell Physiol Biochem

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K⁺-channels fulfill several important functions in the mammalian kidney such as volume regulation, recirculation and secretion of K⁺ ions, and maintaining the resting potential. In this study we used immunocytochemical methods, in situ hybridization, and nephron segment-specific RT-PCR to obtain a detailed picture of the cellular localization of two tandem pore domain potassium (K_2P) channels, THIK-1 (K_2P13.1, KCNK13) and THIK-2 (K_2P12.1, KCNK12). Monospecific antibodies against C-terminal domains of rat THIK-1 and THIK-2 proteins (GST-fusion proteins) were raised in rabbits, freed from cross-reactivity, and affinity purified. All antibodies were validated by Western blot analysis, competitive ELISA, and preabsorption experiments. The expression of THIK channels in specific nephron segments was confirmed by double staining with marker proteins. Results indicate that in rat and mouse THIK-1 and THIK-2 were expressed in the proximal tubule (PT), thick ascending limb (TAL), connecting tubule (CNT), and cortical collecting duct (CCD). In human kidney THIK-1 and THIK-2 were localized in PT, TAL and CCD. Immunostaining of rat tissue revealed an intracellular expression of THIK-1 and THIK-2 throughout the identified nephron segments. However in mouse kidney THIK-2 was identified in basolateral membranes. Overall, the glomerulus, thin limbs and medullary collecting ducts were devoid of THIK-1 and THIK-2 signal. In summary, THIK-1 and THIK-2 are abundantly expressed in the proximal and distal nephron of the mammalian kidney.

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“…GC-G is also an orphan receptor without known agonist, and it is present in skeletal muscles, lungs, and intestine. Hirsch et al (21) showed for the first time the presence of GC-G also in the kidney and identified this guanylate cyclase as the only membrane-bound isoform present in principal cells of rat cortical collecting duct (CCD). Table 1 summarizes the tissue distribution and known agonists for the eight guanylate cyclases identified (22,23).…”

Section: Guanylate Cyclasesmentioning

confidence: 99%

“…The concentration of UGN in the urine correlates with that of urinary cGMP, which again supports the hypothesis that cGMP and the GC-C signaling pathways are activated by UGN at least in the cells of the proximal tubule. However, another possible source of cGMP in the urine could be the activation of other members of the guanylate cyclase family, such as the orphan receptor GC-G, which is present in the luminal membrane of principal cells of rat and mouse CCD (21,57). The source of guanylin peptides in the tubular lumen besides glomerular filtration from the circulation could also be tubular cells because mRNA for GN and UGN is also expressed in kidney epithelial cells (54,58,59).…”

Section: Signaling Mechanisms Of Guanylin Peptides In the Kidneymentioning

confidence: 99%

“…The receptor that is activated by guanylin peptides in the mouse CCD and leads to cGMP and PKG activation is still not identified. A possible candidate for this receptor is the orphan receptor guanylate cyclase G (21,57). Activation of this pathway results in activation of cGMP-dependent K ϩ channels in the basolateral membrane of principal cells and cell hyperpolarization.…”

Section: Signaling Mechanisms Of Guanylin Peptides In the Kidneymentioning

confidence: 99%

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Cellular Effects of Guanylin and Uroguanylin

Sinđić

Schlatter

2006

Journal of the American Society of Nephrology

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Ingestion of a salty meal induces secretion of guanylin (GN) and uroguanylin (UGN) into the intestinal lumen, where they inhibit Na ؉ absorption and induce Cl ؊ , HCO 3 ؊ , and water secretion. Simultaneously, these hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis. GN and UGN therefore participate in the prevention of hypernatremia and hypervolemia after salty meals. The signaling pathway of GN and UGN in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C), which leads to cGMP-dependent inhibition of Na ؉ /H ؉ exchange and activation of the cystic fibrosis transmembrane regulator. In GC-C-deficient mice, GN and UGN still produce renal natriuresis, kaliuresis, and diuresis, suggesting different signaling pathways in the kidney compared with the intestine. Signaling pathways for GN and UGN in the kidney differ along the various nephron segments. In proximal tubule cells, a cGMP-and GC-C-dependent signaling was demonstrated for both peptides. In addition, UGN activates a pertussis toxinsensitive G-protein-coupled receptor. A similar dual signaling pathway is also known for atrial natriuretic peptide. Recently, a cGMP-independent signaling pathway for GN and UGN was also shown in principal cells of the human and mouse cortical collecting duct. Because GN and UGN activate different signaling pathways in specific organs and even within the kidney, this review focuses on more recent findings on cellular effects and signaling mechanisms of these peptides and their pathophysiologic implications in the intestine and the kidney.

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Cellular localization, membrane distribution, and possible function of guanylyl cyclases A and 1 in collecting ducts of rat

Cited by 16 publications

References 46 publications

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Disruption of Guanylyl Cyclase-G Protects against Acute Renal Injury

Cellular Localization of THIK-1 (K<sub>2P</sub>13.1) and THIK-2 (K<sub>2P</sub>12.1) K<sup>+</sup> Channels in the Mammalian Kidney

Cellular Effects of Guanylin and Uroguanylin

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