共查询到20条相似文献,搜索用时 31 毫秒
1.
Iandiev I Wurm A Pannicke T Wiedemann P Reichenbach A Robson SC Zimmermann H Bringmann A 《Purinergic signalling》2007,3(4):423-433
Extracellular nucleotides mediate glia-to-neuron signalling in the retina and are implicated in the volume regulation of retinal
glial (Müller) cells under osmotic stress conditions. We investigated the expression and functional role of ectonucleotidases
in Müller cells of the rodent retina by cell-swelling experiments, calcium imaging, and immuno- and enzyme histochemistry.
The swelling of Müller cells under hypoosmotic stress was inhibited by activation of an autocrine purinergic signalling cascade.
This cascade is initiated by exogenous glutamate and involves the consecutive activation of P2Y1 and adenosine A1 receptors, the action of ectoadenosine 5′-triphosphate (ATP)ases, and a nucleoside-transporter-mediated
release of adenosine. Inhibition of ectoapyrases increased the ATP-evoked calcium responses in Müller cell endfeet. Müller
cells were immunoreactive for nucleoside triphosphate diphosphohydrolases (NTPDase)2 (but not NTPDase1), ecto-5′-nucleotidase,
P2Y1, and A1 receptors. Enzyme histochemistry revealed that ATP but not adenosine 5′-diphosphate (ADP) is extracellularly metabolised
in retinal slices of NTPDase1 knockout mice. NTPDase1 activity and protein is restricted to blood vessels, whereas activity
of alkaline phosphatase is essentially absent at physiological pH. The data suggest that NTPDase2 is the major ATP-degrading
ectonucleotidase of the retinal parenchyma. NTPDase2 expressed by Müller cells can be implicated in the regulation of purinergic
calcium responses and cellular volume. 相似文献
2.
Gennady G. Yegutkin 《Critical reviews in biochemistry and molecular biology》2014,49(6):473-497
AbstractExtracellular nucleotides and nucleosides mediate diverse signaling effects in virtually all organs and tissues. Most models of purinergic signaling depend on functional interactions between distinct processes, including (i) the release of endogenous ATP and other nucleotides, (ii) triggering of signaling events via a series of nucleotide-selective ligand-gated P2X and metabotropic P2Y receptors as well as adenosine receptors and (iii) ectoenzymatic interconversion of purinergic agonists. The duration and magnitude of purinergic signaling is governed by a network of ectoenzymes, including the enzymes of the nucleoside triphosphate diphosphohydrolase (NTPDase) family, the nucleotide pyrophosphatase/phosphodiesterase (NPP) family, ecto-5′-nucleotidase/CD73, tissue-nonspecific alkaline phosphatase (TNAP), prostatic acid phosphatase (PAP) and other alkaline and acid phosphatases, adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). Along with “classical” inactivating ectoenzymes, recent data provide evidence for the co-existence of a counteracting ATP-regenerating pathway comprising the enzymes of the adenylate kinase (AK) and nucleoside diphosphate kinase (NDPK/NME/NM23) families and ATP synthase. This review describes recent advances in this field, with special emphasis on purine-converting ectoenzymes as a complex and integrated network regulating purinergic signaling in such (patho)physiological states as immunomodulation, inflammation, tumorigenesis, arterial calcification and other diseases. The second part of this review provides a comprehensive overview and basic principles of major approaches employed for studying purinergic activities, including spectrophotometric Pi-liberating assays, high-performance liquid chromatographic (HPLC) and thin-layer chromatographic (TLC) analyses of purine substrates and metabolites, capillary electrophoresis, bioluminescent, fluorometric and electrochemical enzyme-coupled assays, histochemical staining, and further emphasizes their advantages, drawbacks and suitability for assaying a particular catalytic reaction. 相似文献
3.
Larisa Bulavina Frank Szulzewsky Adriana Rocha Grietje Krabbe Simon C. Robson Vitali Matyash Helmut Kettenmann 《Purinergic signalling》2013,9(2):199-205
Purinergic signaling plays a major role in the regulation of phagocytosis in microglia. Interplay between P2 and P1 receptor activation is controlled by a cascade of extracellular enzymes which dephosphorylate purines resulting in the formation of adenosine. The ATP- and ADP-degrading capacity of cultured microglia depends on the expression of ecto-nucleoside triphosphate diphosphohydrolase 1 (CD39) and is several times higher when compared to astrocytes which lack this enzyme. In brain slices, deletion of CD39 resulted in a 50 % decrease of ADP-degrading ability, while the degradation of ATP was decreased to about 75 % of the values measured in wild-type brain tissue. Microglia in acute slices from cd39?/? animals had increased constitutive phagocytic activity which could not be further enhanced by ATP in contrast to control animals. Pharmacological blockage of P2 receptors decreased the constitutive phagocytic activity to a similar base level in wild-type and cd39?/? microglia. Activation of P1 receptors by non-hydrolysable adenosine analog significantly decreased phagocytic activity. Deletion of CD73, an enzyme expressed by microglia which converts AMP to adenosine did not affect phagocytic activity. Taken together, these data show that CD39 plays a prominent role in controlling ATP levels and thereby microglial phagocytosis. 相似文献
4.
Kittel A Csapó ZS Csizmadia E Jackson SW Robson SC 《European journal of histochemistry : EJH》2004,48(3):253-259
Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) is the dominant ecto-nucleotidase of vascular and placental trophoblastic tissues and appears to modulate the functional expression of type-2 purinergic (P2) G-protein coupled receptors (GPCRs). Hence, this ectoenzyme could regulate nucleotide-mediated signalling events in placental tissue. This immunohistochemical and immuno-electron microscopic study demonstrates the expression of NTPDase1/CD39, P2Y1 and P2Y2 receptors in different cell types of human placenta. Specifically P2Y1 has an exclusive vascular distribution whereas P2Y2 is localized on trophoblastic villi. Co-localization of P2Y1 and NTPDase1/CD39 are observed in caveolae, membrane microdomains of endothelial cells. The differential localization of these P2 receptors might indicate their unique roles in the regulation of extracellular nucleotide concentrations in human placental tissues and consequent effects on vascular tone and blood fluidity. 相似文献
5.
Fausther M Lecka J Soliman E Kauffenstein G Pelletier J Sheung N Dranoff JA Sévigny J 《American journal of physiology. Gastrointestinal and liver physiology》2012,302(4):G447-G459
Ectonucleotidases modulate purinergic signaling by hydrolyzing ATP to adenosine. Here we characterized the impact of the cellular distribution of hepatic ectonucleotidases, namely nucleoside triphosphate diphosphohydrolase (NTPDase)1/CD39, NTPDase2/CD39L1, NTPDase8, and ecto-5'-nucleotidase/CD73, and of their specific biochemical properties, on the levels of P1 and P2 receptor agonists, with an emphasis on adenosine-producing CD73. Immunostaining and enzyme histochemistry showed that the distribution of CD73 (protein and AMPase activity) overlaps partially with those of NTPDase1, -2, and -8 (protein levels and ATPase and ADPase activities) in normal rat liver. CD73 is expressed in fibroblastic cells located underneath vascular endothelial cells and smooth muscle cells, which both express NTPDase1, in portal spaces in a distinct fibroblast population next to NTPDase2-positive portal fibroblasts, and in bile canaliculi, together with NTPDase8. In fibrotic rat livers, CD73 protein expression and activity are redistributed but still overlap with the NTPDases mentioned. The ability of the observed combinations of ectonucleotidases to generate adenosine over time was evaluated by reverse-phase HPLC with the recombinant rat enzymes at high "inflammatory" (500 μM) and low "physiological" (1 μM) ATP concentrations. Overall, ATP was rapidly converted to adenosine by the NTPDase1+CD73 combination, but not by the NTPDase2+CD73 combination. In the presence of NTPDase8 and CD73, ATP was sequentially dephosphorylated to the CD73 inhibitor ADP, and then to AMP, thus resulting in a delayed formation of adenosine. In conclusion, the specific cellular cocompartmentalization of CD73 with hepatic NTPDases is not redundant and may lead to the differential activation of P1 and P2 receptors, under normal and fibrotic conditions. 相似文献
6.
Faria M Magalhães-Cardoso T Lafuente-de-Carvalho JM Correia-de Sá P 《Nucleosides, nucleotides & nucleic acids》2008,27(6):761-768
Vascular responses to adenine nucleotides in human corpora cavernosa from men with vasculogenic erectile dysfunction were investigated. We also evaluated the catabolism of extracellular adenine nucleotides to probe its relevance to vascular hemodynamics in impotent men. Human corpora cavernosa have high NTPDase1/CD39 activity, converting ATP directly into AMP, without significant ADP formation. Extracellular ATP hydrolysis is slower in impotent patients. Adenine nucleotides have dual roles on phenylephrine-contracted strips of corpora cavernosa operated by P2X-contractant and P2Y-relaxant receptors. Prolonged exposure to endogenous ATP related to decreased NTPDase1/CD39 activity leads to P2-purinoceptor desensitization in impotent men. Shutting down ATP signaling in vasculogenic impotent men may represent a defense mechanism for preventing purinergic overstimulation. 相似文献
7.
M. Faria T. Magalhães-Cardoso J.-M. Lafuente-de-Carvalho P. Correia-de Sá 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):761-768
Vascular responses to adenine nucleotides in human corpora cavernosa from men with vasculogenic erectile dysfunction were investigated. We also evaluated the catabolism of extracellular adenine nucleotides to probe its relevance to vascular hemodynamics in impotent men. Human corpora cavernosa have high NTPDase1/CD39 activity, converting ATP directly into AMP, without significant ADP formation. Extracellular ATP hydrolysis is slower in impotent patients. Adenine nucleotides have dual roles on phenylephrine-contracted strips of corpora cavernosa operated by P2X-contractant and P2Y-relaxant receptors. Prolonged exposure to endogenous ATP related to decreased NTPDase1/CD39 activity leads to P2-purinoceptor desensitization in impotent men. Shutting down ATP signaling in vasculogenic impotent men may represent a defense mechanism for preventing purinergic overstimulation. 相似文献
8.
Braganhol E Zanin RF Bernardi A Bergamin LS Cappellari AR Campesato LF Morrone FB Campos MM Calixto JB Edelweiss MI Wink MR Sévigny J Robson SC Battastini AM 《Purinergic signalling》2012,8(2):235-243
Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression. 相似文献
9.
Schicker K Hussl S Chandaka GK Kosenburger K Yang JW Waldhoer M Sitte HH Boehm S 《Biochimica et biophysica acta》2009,1793(2):325-334
Most cells express more than one receptor plus degrading enzymes for adenine nucleotides or nucleosides, and cellular responses to purines are rarely compatible with the actions of single receptors. Therefore, these receptors are viewed as components of a combinatorial receptor web rather than self-dependent entities, but it remained unclear to what extent they can associate with each other to form signalling units. P2Y(1), P2Y(2), P2Y(12), P2Y(13), P2X(2), A(1), A(2A) receptors and NTPDase1 and -2 were expressed as fluorescent fusion proteins which were targeted to membranes and signalled like the unlabelled counterparts. When tested by FRET microscopy, all the G protein-coupled receptors proved able to form heterooligomers with each other, and P2Y(1), P2Y(12), P2Y(13), A(1), A(2A), and P2X(2) receptors also formed homooligomers. P2Y receptors did not associate with P2X, but G protein-coupled receptors formed heterooligomers with NTPDase1, but not NTPDase2. The specificity of prototypic interactions (P2Y(1)/P2Y(1), A(2A)/P2Y(1), A(2A)/P2Y(12)) was corroborated by FRET competition or co-immunoprecipitation. These results demonstrate that G protein-coupled purine receptors associate with each other and with NTPDase1 in a highly promiscuous manner. Thus, purinergic signalling is not only determined by the expression of receptors and enzymes but also by their direct interaction within a previously unrecognized multifarious membrane network. 相似文献
10.
11.
Localization of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and NTPDase2 in pancreas and salivary gland. 总被引:3,自引:0,他引:3
Agnes Kittel Julie Pelletier Fran?ois Bigonnesse Olaf Guckelberger Krisztina Kordás Norbert Braun Simon C Robson Jean Sévigny 《The journal of histochemistry and cytochemistry》2004,52(7):861-871
Ectonucleoside 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(-/-) 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. 相似文献
12.
Chiara Zoppellaro Anna Bin Paola Brun Serena Banzato Veronica Macchi Ignazio Castagliuolo Maria Cecilia Giron 《PloS one》2013,8(8)
Adenosine plays an important role in regulating intestinal motility and inflammatory processes. Previous studies in rodent models have demonstrated that adenosine metabolism and signalling are altered during chronic intestinal inflammatory diseases. However, the involvement of the adenosinergic system in the pathophysiology of gut dysmotility associated to a primary neurodysfunction is still unclear. Recently, we showed that the neurotropic Herpes simplex virus type-1 (HSV-1), orally inoculated to rodents, infects the rat enteric nervous system (ENS) and affects gut motor function without signs of systemic infection. In this study we examined whether changes in purinergic metabolism and signaling occur during permanent HSV-1 infection of rat ENS. Using isolated organ bath assays, we found that contraction mediated by adenosine engagement of A1 or A2A receptors was impaired at 1 and 6 weeks post-viral administration. Immunofluorescence studies revealed that viral infection of ENS led to a marked redistribution of adenosine receptors: A1 and A2B receptors were confined to the muscle layers whereas A2A and A3 receptors were expressed mainly in the myenteric plexus. Viral-induced ENS neurodysfunction influenced adenosine metabolism by increasing adenosine deaminase and CD73 levels in longitudinal muscle-myenteric plexus with no sign of frank inflammation. This study provides the first evidence for involvement of the adenosinergic system during HSV-1 infection of the ENS. As such, this may represent a valid therapeutic target for modulating gut contractility associated to a primary neurodysfunction. 相似文献
13.
Extracellular nucleotide signaling in adult neural stem cells: synergism with growth factor-mediated cellular proliferation 总被引:10,自引:0,他引:10
Mishra SK Braun N Shukla V Füllgrabe M Schomerus C Korf HW Gachet C Ikehara Y Sévigny J Robson SC Zimmermann H 《Development (Cambridge, England)》2006,133(4):675-684
We have previously shown that the extracellular nucleoside triphosphate-hydrolyzing enzyme NTPDase2 is highly expressed in situ by stem/progenitor cells of the two neurogenic regions of the adult murine brain: the subventricular zone (type B cells) and the dentate gyrus of the hippocampus (residual radial glia). We explored the possibility that adult multipotent neural stem cells express nucleotide receptors and investigated their functional properties in vitro. Neurospheres cultured from the adult mouse SVZ in the presence of epidermal growth factor and fibroblast growth factor 2 expressed the ecto-nucleotidases NTPDase2 and the tissue non-specific isoform of alkaline phosphatase, hydrolyzing extracellular ATP to adenosine. ATP, ADP and, to a lesser extent, UTP evoked rapid Ca(2+) transients in neurospheres that were exclusively mediated by the metabotropic P2Y(1) and P2Y(2) nucleotide receptors. In addition, agonists of these receptors and low concentrations of adenosine augmented cell proliferation in the presence of growth factors. Neurosphere cell proliferation was attenuated after application of the P2Y(1)-receptor antagonist MRS2179 and in neurospheres from P2Y(1)-receptor knockout mice. In situ hybridization identified P2Y(1)-receptor mRNA in clusters of SVZ cells. Our results infer nucleotide receptor-mediated synergism that augments growth factor-mediated cell proliferation. Together with the in situ data, this supports the notion that extracellular nucleotides contribute to the control of adult neurogenesis. 相似文献
14.
Amel Rayah Jean M. Kanellopoulos Francesco Di Virgilio 《Microbes and infection / Institut Pasteur》2012,14(14):1254-1262
Immune cells express receptors for extracellular nucleotides named P2 receptors. P2 receptors transduce signals delivered by nucleotides present in the extracellular environment. Accruing evidence shows that purinergic signalling has a profound effect on multiple immune cell responses such as T lymphocyte proliferation, chemotaxis, cytokine release, phagocytosis, Ag presentation and cytotoxicity. This makes P2 receptors an attractive target for the therapy of immuno-mediated disease and cancer. 相似文献
15.
Jing Guo Peng Yang Yi-Fan Li Jin-Fan Tang Zhao-Xuan He Shu-Guang Yu Hai-Yan Yin 《Purinergic signalling》2023,19(1):329
Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73. 相似文献
16.
Mary G. O’Keeffe Peter R. Thorne Gary D. Housley Simon C. Robson Srdjan M. Vlajkovic 《Histochemistry and cell biology》2010,133(4):425-436
Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate complex extracellular P2 receptor signalling pathways
in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from this family
(NTPDase1-8) are expressed in the adult rat cochlea. This study reports the changes in expression of NTPDase5 and NTPDase6
in the developing rat cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and
show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal
patterns for NTPDase5 and NTPDase6 expression during cochlear development, which are indicative of both cytosolic and extracellular
action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting
Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is
confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisation in the developing cochlea underpins
its putative role in hair cell bundle development, probably via cytosolic action, whilst NTPDase5 may have a broader extracellular
role in the development of sensory and neural tissues in the rat cochlea. Both NTPDase5 and NTPDase6 colocalize with UDP-preferring
P2Y4, P2Y6 and P2Y14 receptors during cochlear development, but this strong association was lost in the adult cochlea. Spatiotemporal topographic
expression of NTPDase5 and NTPDase6 and P2Y receptors in adult and developing cochlear tissues provide strong support for
the role of pyrimidinergic signalling in cochlear development. 相似文献
17.
Hui-quan Li Cong Chen Ying Dou Hang-jun Wu Yi-jun Liu Hui-Fang Lou Jian-min Zhang Xiao-ming Li Hao Wang Shumin Duan 《Molecular and cellular biology》2013,33(21):4282-4293
Brain disturbances, like injuries or aberrant protein deposits, evoke nucleotide release or leakage from cells, leading to microglial chemotaxis and ingestion. Recent studies have identified P2Y12 purinergic receptors as triggers for microglial chemotaxis and P2Y6 receptors as mediators for phagocytosis. However, pinocytosis, known as the internalization of fluid-phase materials, has received much less attention. We found that ATP efficiently triggered pinocytosis in microglia. Pharmacological analysis and knockdown experiments demonstrated the involvement of P2Y4 receptors and the phosphatidylinositol 3-kinase/Akt cascade in the nucleotide-induced pinocytosis. Further evidence indicated that soluble amyloid beta peptide 1-42 induced self-uptake in microglia through pinocytosis, a process involving activation of P2Y4 receptors by autocrine ATP signaling. Our results demonstrate a previously unknown function of ATP as a “drink me” signal for microglia and P2Y4 receptors as a potential therapeutic target for the treatment of Alzheimer''s disease. 相似文献
18.
Mary G. O’Keeffe Peter R. Thorne Gary D. Housley Simon C. Robson Srdjan M. Vlajkovic 《Purinergic signalling》2010,6(2):249-261
Membrane-bound ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) in the inner ear regulate complex extracellular
purinergic type-2 (P2) receptor signalling pathways through hydrolysis of extracellular nucleoside 5′-triphosphates and diphosphates.
This study investigated the distribution of NTPDase5 and NTPDase6, two intracellular members of the E-NTPDase family, and
linked this to regulation of P2 receptor signalling in the adult rat cochlea. These extracellular ectonucleotidases preferentially
hydrolyse nucleoside 5′-diphosphates such as UDP and GDP. Expression of both enzymes at mRNA and protein level was detected
in cochlear tissues and there was in vivo release of soluble NTPDase5 and 6 into cochlear fluids. Strong NTPDase5 immunostaining
was found in the spiral ganglion neurones and supporting Deiters’ cells of the organ of Corti, while NTPDase6 was confined
to the inner hair cells. Upregulation of NTPDase5 after exposure to loud sound indicates a dynamic role for NTPDase5 in cochlear
response to stress, whereas NTPDase6 may have more limited extracellular roles. Noise-induced upregulation of co-localised
UDP-preferring P2Y6 receptors in the spiral ganglion neurons further supports the involvement of NTPDase5 in regulation of P2Y receptor signalling.
Noise stress also induced P2Y14 (UDP- and UDP-glucose preferring) receptor expression in the root processes of the outer sulcus cells, but this was not associated
with localization of the E-NTPDases. 相似文献
19.
CD39 modulates endothelial cell activation and apoptosis 总被引:4,自引:0,他引:4
Goepfert C Imai M Brouard S Csizmadia E Kaczmarek E Robson SC 《Molecular medicine (Cambridge, Mass.)》2000,6(7):591-603
20.
Reigada D Lu W Zhang X Friedman C Pendrak K McGlinn A Stone RA Laties AM Mitchell CH 《American journal of physiology. Cell physiology》2005,289(3):C617-C624
Stimulation of ATP or adenosine receptors causes important physiological changes in retinal pigment epithelial (RPE) cells that may influence their relationship to the adjacent photoreceptors. While RPE cells have been shown to release ATP, the regulation of extracellular ATP levels and the production of dephosphorylated purines is not clear. This study examined the degradation of ATP by RPE cells and the physiological effects of the adenosine diphosphate (ADP) that result. ATP was readily broken down by both cultured human ARPE-19 cells and the apical membrane of fresh bovine RPE cells. The compounds ARL67156and -mATP inhibited this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA message for multiple extracellular degradative enzymes; ectonucleotide pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca2+. Both responses were inhibited by thapsigargin and P2Y1 receptor inhibitor MRS 2179. Message for both P2Y1 and P2Y12 receptors was detected in ARPE-19 cells. These results suggest that extracellular degradation of ATP in subretinal space can result in the production of ADP. This ADP can stimulate P2Y receptors and augment Ca2+ signaling in the RPE. ectoapyrase; PC-1; CD39; CD39L1; P2Y1; P2Y12; ADP; ATP release; photoreceptors; retinal detachment 相似文献