Atrial natriuretic peptide stimulates Cl<sup>-</sup>transport in retinal pigment epithelial cells

Mikami, Yoshito; Hara, Mitsuyoshi; Yasukura, Tohru; Uyama, M; Minato, Akio; Inagaki, Chiyoko

doi:10.3109/02713689508999937

Cited by 15 publications

(7 citation statements)

References 23 publications

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“…ANP is furthermore involved in controlling the extracellular fluid homeostasis. Also in RPE cells it has been shown that ANP stimulates Cl -transport [27] .…”

Section: Discussionmentioning

confidence: 99%

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

et al. 2006

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Background/Aims: Cyclic 3′,5′-guanosine monophosphate (cGMP), a central molecule in the phototransduction cascade, is also involved in a number of other physiological processes in the retina, like stimulating the absorption of subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump. The aim of this study was to quantify cGMP synthesis by RPE cells and to investigate the role of two separate enzymatic pathways (soluble versus particulate guanylyl cyclase) in its production. Methods: cGMP expression was evaluated by immunochemistry and radioimmunoassay following culture of the D407 RPE cell line in the presence of a nonselective phosphodiesterase inhibitor (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). Results: Stimulation of the particulate guanylyl cyclase in RPE cells with ANP resulted in high intra- and extracellular cGMP levels. Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation of cGMP levels compared to controls. Conclusions: These results show that cultured human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the particulate guanylyl cyclase pathway.

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“…ANP is furthermore involved in controlling the extracellular fluid homeostasis. Also in RPE cells it has been shown that ANP stimulates Cl -transport [27] .…”

Section: Discussionmentioning

confidence: 99%

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

et al. 2006

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“…Indeed, it has actually been suggested for over a decade that ANF might have noncardiovascular autocrine and paracrine functions (13). Epithelial ANF may have a physiological role in the regulation of fluid secretion of the lacrimal and submaxillary glands and ducts analogous to its cardiovascular fluid homeostasis role (15,50,51). Thus, regulation of ANF expression by PITX2 and MEF2A may contribute to oral epithelial physiology.…”

Section: Discussionmentioning

confidence: 99%

Cell-specific Activation of the Atrial Natriuretic Factor Promoter by PITX2 and MEF2A

Toro¹,

Saadi²,

Kuburas

et al. 2004

Journal of Biological Chemistry

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The PITX2 homeodomain protein is mutated in patients with Axenfeld-Rieger syndrome and is involved in the development of multiple organ systems, including the heart. We have examined the interaction of PITX2 isoforms with myocyte-enhancing factor 2A (MEF2A), which is a known regulator of cardiac development. A direct interaction between PITX2a and MEF2A was demonstrated using yeast two-hybrid and GST pulldown assays. To study the functional significance of this interaction, we used the atrial natriuretic factor (ANF) promoter. Coexpression of MEF2A and PITX2a or Pitx2c resulted in a strong synergistic activation of the ANF promoter in LS8 oral epithelial cells but not in other cell lines (NIH/3T3, Chinese hamster ovary, or C2C12). The synergism was dependent on promoter context, because it required MEF2 binding sites and was not seen with two other PITX2 target promoters. DNA binding by MEF2A was required but not sufficient for synergism. Upstream activators of p38 MAP kinases, MKK3 and MKK6, increased PITX2a and Pitx2c activity to yield up to 90-fold activation of the ANF promoter in LS8 cells. Because Axenfeld-Rieger syndrome is autosomal dominant and affects development of the oral epithelium, we tested one of the known PITX2 mutants. The PITX2a-K88E mutant protein suppressed wild type PITX2a synergism with MEF2A. These results demonstrate a promoter-and cell-specific functional interaction between PITX2 and MEF2A and suggest the possibility of coordinate control by these factors in the oral epithelium.The PITX2 gene was cloned based on its linkage in AxenfeldRieger syndrome (ARS) 1 (1). ARS is an autosomal dominant human disorder characterized by ocular anterior chamber anomalies causing glaucoma in Ͼ50% of affected individuals as well as dental hypoplasia, mild craniofacial dysmorphism, and umbilical stump abnormalities (1-3). Other features associated with this syndrome include abnormal cardiac, limb, and pituitary development. PITX2 is a member of the bicoid/paired-like homeodomain family (3, 4). There are three isoforms, PITX2a, b, c, that differ only in their amino-terminal regions. The Pitx2 knock-out mouse is lethal at embryonic day 15 because of cardiac abnormalities and shows defects in cardiac positioning, atrial septation, and outflow tract development (4). Pitx2 is a proliferation target in the Wnt/Dvl pathway, which, when disrupted, leads to cardiac outflow tract abnormalities (5). Pitx2 has also been shown to be a downstream target in left-right asymmetry pathways and organogenesis (6 -9). It is expressed asymmetrically on the left side of the lateral plate mesoderm and derivative organs, including the heart and the gut.We have used the yeast two-hybrid assay to analyze candidate PITX2 interacting partners. With respect to the role of PITX2 in heart development, we were intrigued by the recent findings that PITX2 could activate the promoter of the atrial natriuretic factor (ANF) gene (10). ANF plays a key role in electrolyte and fluid homeostasis in the cardiovascular system by causing natriure...

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“…cGMP might play a role in both these processes. It has been shown that ANP stimulates Cl -transport in RPE cells [12] . mRNA of NPR-A and NPR-B, both ANP receptors, has been demonstrated in cultured rabbit RPE cells [9] .…”

Section: Discussionmentioning

confidence: 99%

“…cGMP in RPE cells has been implicated in the stimulation of Cl -transport, suppression of hypoxia-associated vascular endothelial growth factor (VEGF) gene expression, and phagocytosis of rod outer segments [6,7,12] . The Cl -transport was stimulated by ANP and by NO, suggesting that there is no selective GCstimulating pathway regulating this RPE cell property [12] . VEGF gene expression was studied only as a sodium nitroprusside (SNP)-mediated effect [7] .…”

Section: Introductionmentioning

confidence: 99%

Two Autocrine Pathways to Regulate Cyclic GMP Synthesis in Cultured Human Retinal Pigment Epithelial Cells

et al. 2008

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Aim: To investigate the role of two separate enzymatic pathways [soluble (sGC) vs. particulate (pGC) guanylyl cyclase] in the synthesis of cyclic GMP (cGMP) in cultured human retinal pigment epithelial (RPE) cells. Methods: cGMP accumulation was evaluated by quantitative analysis of cGMP immunoreactivity. RPE cells were also stained for inducible nitric oxide synthase (iNOS), ANP and β₁- and α₂-subunits of sGC. Results: We showed nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and iNOS immunoreactivity in RPE cells. Incubation of the cells in the presence of 1 mM IBMX to inhibit phosphodiesterase activity, and the simultaneous inhibition of NOS activity with L-NAME suggested the involvement of sGC in maintaining a low level of cGMP in the RPE cells. The involvement of sGC was further supported by detection of the β₁- and α₂-subunits of sGC. Incubation of the cells in the presence of atrial natriuretic peptide (ANP) to stimulate pGC strongly increased cGMP immunoreactivity. We also demonstrated the presence of ANP in all RPE cells. Conclusion: Cultured human RPE cells are capable of producing cGMP after stimulation of sGC or pGC. The presence of iNOS and ANP in all cells suggests two different autocrine pathways of stimulating cGMP production in these cells. The possible role of cGMP in the regulation iNOS gene expression and in the regulation of ANP is discussed.

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Atrial natriuretic peptide stimulates Cl^-transport in retinal pigment epithelial cells

Cited by 15 publications

References 23 publications

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

Cell-specific Activation of the Atrial Natriuretic Factor Promoter by PITX2 and MEF2A

Two Autocrine Pathways to Regulate Cyclic GMP Synthesis in Cultured Human Retinal Pigment Epithelial Cells

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Atrial natriuretic peptide stimulates Cl-transport in retinal pigment epithelial cells

Cited by 15 publications

References 23 publications

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

Cell-specific Activation of the Atrial Natriuretic Factor Promoter by PITX2 and MEF2A

Two Autocrine Pathways to Regulate Cyclic GMP Synthesis in Cultured Human Retinal Pigment Epithelial Cells

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Atrial natriuretic peptide stimulates Cl^-transport in retinal pigment epithelial cells