Localization of NTPDase1/CD39 in Normal and Transformed Human Pancreas

Kittel, Ágnes; Garrido, Marta; Varga, Gábor

doi:10.1177/002215540205000412

Cited by 31 publications

(25 citation statements)

References 36 publications

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“…Like our findings, an immunohistochemical study showed that apical and basolateral membranes of the acinar cells in pig pancreas were immunoreactive for an antibody directed against the common apyrase conserved region 4 (ACR 4) of NTPDase molecules (Sevigny et al 1998). However, in human pancreatic cryosections, according to electron microscopic staining, acini were devoid of NTPDase1 immunoreactivity or ATPase activity (Kittel et al 2002). Only the duct cells showed immunoreactivity for NTPDase1.…”

Section: Discussionsupporting

confidence: 83%

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Kittel

Pelletier²,

Bigonnesse

et al. 2004

J Histochem Cytochem.

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S U M M A R YEctonucleoside triphosphate diphosphohydrolases (NTPDases) are membrane-bound ectoenzymes that hydrolyze extracellular nucleotides. We investigated the distribution of NTPDase1 and NTPDase2 in murine salivary gland and pancreas. Histochemistry and immunostaining (by both light and electron microscopy), combined with functional assays, were used to describe the localization patterns and enzyme activities in the organs of wild-type and NTPDase1/cd39-null mice. Pancreatic acinar cells and salivary gland acinar/myoepithelial cells were positive for NTPDase1 and NTPDase2. Ecto-ATPase activity was slightly higher in salivary glands. Ductal epithelial cells expressed ecto-ATPase activity but NTPDase1 and NTPDase2 expression were weak at best. ATPase activity was found in blood vessels of both tissues and its localization pattern overlapped with NTPDase1 staining. In these structures, NTPDase2 antibodies stained the basolateral aspect of endothelial cells and the supporting cells. Biochemical assays and histochemical staining showed relatively high levels of ATPase activity in both glands of cd39 Ϫ / Ϫ mice. Our data therefore support a physiological role for NTPDase2 and other ectonucleotidases in the pancreas and salivary glands. Because NTPDase1 is expressed in non-vascular cell types, this finding suggests that NTPDase1 may have functions in the gastrointestinal tract that differ from those demonstrated in the vascular system.

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Section: Discussionsupporting

confidence: 83%

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Kittel

Pelletier²,

Bigonnesse

et al. 2004

J Histochem Cytochem.

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“…According to our previous results, NTPDase1 is concentrated in caveolae of several types of cells including endothelial and smooth muscle cells (Kittel et al , 2002(Kittel et al , 2004Koziak et al 2000) and this is also confirmed in our present experiments. Interestingly, while distribution of NTPDase1 has changed in pathological tissue, the relative amount or distribution of its scaffolding protein caveolin-1, which was also demonstrated in myocytes, has not changed with age or under ischemic conditions.…”

Section: Discussionsupporting

confidence: 93%

Expression of NTPDase1 and caveolins in human cardiovascular disease

Kittel

Kiss

Müllner

et al. 2005

Histochem Cell Biol

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Pathological circumstances like inflammation or ischemic insult facilitate the release of adenine nucleotides from several types of cells. These extracellular nucleotides are rapidly converted to adenosine by ectonucleotidases, mainly ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) and CD73. NTPDase1/CD39 can interact with caveolins, structural proteins of signal-transducing microdomains termed caveolae. Caveolins are thought to have physiological roles in heart ageing and cardiac diseases. The aim of this study was to investigate the expression of NTPDase1 together with caveolins in chronic human cardiovascular diseases and elucidate their role in human heart. The HPLC analysis showed significant increase in ATPase activity in pathological samples from patients with ischemic heart disease. Immunostaining also showed alterations in the expression and distribution of NTPDase1. Caveolin-1 and caveolin-2 expression was much alike in control and pathological cases, while expression of caveolin-3 was lower in pathological samples. Changes in the expression of NTPDase1 and caveolins seem to be independent of human cardiovascular disease.

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“…Ecto-ATPases are crucial in the duration and magnitude of purinergic signaling (39). A functional apyrase (CD39) has been shown to be expressed in human β cells (40). Application of the apyrase inhibitor ARL67156 (50 μM) (41, 42) increased basal insulin secretion from islets incubated at low glucose concentration (3 mM; Fig.…”

Section: Resultsmentioning

confidence: 95%

ATP-gated P2X ₃ receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell

Jacques-Silva

Correa-Medina

Cabrera

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

117

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Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human β cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca 2+ concentration, [Ca 2+ ] i , and hormone release in vitro, we show that human β cells express ionotropic ATP receptors of the P2X 3 type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X 3 receptors in the β-cell plasma membrane, resulting in increased [Ca 2+ ] i and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the β cell's secretory machinery. This may explain how the human pancreatic β cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo.extracellular ATP | human pancreatic β cell | insulin secretion | P2X receptor | positive autocrine feedback G lucose homeostasis is tightly controlled by hormone secretion from the endocrine pancreas, the islets of Langerhans. Even small physiological deviations (e.g., 10%) in plasma glucose are effectively counteracted by sharp (e.g., 3-fold) increases in the secretion of the islet hormones insulin and glucagon (1). Intraislet autocrine and paracrine signaling are pivotal mechanisms for proper function of the islet, making islet cells extremely sensitive and responsive to plasma glucose fluctuations. The roles of different compounds such as GABA, glutamate, Zn 2+ , insulin, and ATP as autocrine and paracrine regulators of islet hormone release have been examined extensively (2-8). Extracellular ATP seems important because it is present in insulin-containing secretory granules and is released during glucose stimulation in sufficient amounts to stimulate ATP receptors (9-12).Extracellular ATP is an important neurotransmitter signal in the brain as well as in vascular, immune, and endocrine cells (13-15). The purinergic system comprises receptors for extracellular ATP and adenosine, the P2 and P1 receptors, respectively. P2 purinergic receptors can be divided into metabotropic P2Y receptors (G protein coupled) and ionotropic P2X receptors (ligand-gated ion channels) (16). The ionotropic P2X family comprises seven subtypes named P2X 1 -P2X 7 that regulate cell function by opening cation channels permeable to Na + , K + , and Ca 2+ (15,17). Activation of these channels regulates the release of neurotransmitters and hormones, either through direct Ca 2+ influx or by promoting membrane depolarization and thereby inducing action potentials (18-21).The role of ATP signaling in the physiology of pancreatic islets has been studied in rodent models, but the results in the literature are conflicting (22-28). In rat islets, purinergic agonists...

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Localization of NTPDase1/CD39 in Normal and Transformed Human Pancreas

Cited by 31 publications

References 36 publications

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Expression of NTPDase1 and caveolins in human cardiovascular disease

ATP-gated P2X ₃ receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell

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Localization of NTPDase1/CD39 in Normal and Transformed Human Pancreas

Cited by 31 publications

References 36 publications

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland

Expression of NTPDase1 and caveolins in human cardiovascular disease

ATP-gated P2X 3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell

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ATP-gated P2X ₃ receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell