Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides

Pearson, Jeremy D.; Gordon, John L.

doi:10.1038/281384a0

Cited by 385 publications

(161 citation statements)

References 18 publications

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“…Participation of this enzyme in the formation of adenosine would depend upon the presence of micromolar concentrations of AMP in extracellular fluids. One developmental process likely to contribute such high levels of extracellular AMP is cell death (Pearson and Gordon, 1979;Gordon, 1986;Papadimitriou et al, 1991). This process has been described in the uterine epithelium (El-Shershaby and Hinchliffe, 1975;Parr and Parr, 1987), primary decidua (Welsh and Enders, 1987;Parr and Parr, 19891, and secondary decidua (Welsh and Enders, 1985;Katz and Abrahamsohn, 1987) during implantation chamber morphogenesis in rodents.…”

Section: Transmural Asymmetry Of Adenosine Concentration Across the Amentioning

confidence: 99%

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Blackburn

Gao

Airhart

et al. 1992

Developmental Dynamics

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Extracellular adenosine has the potential to influence many aspects of target cell metabolism. The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryodecidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5'-nucleotidase (5'-NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4). To measure adenosine levels, nucleoside extracts were etheno-derivatized and quantitated by high-performance liquid chromatography-fluorescence detection (0.03 pmollmg protein sensitivity). Adenosine levels were determined to be 0.18 nmol/mg protein in the nonpregnant uterus; however, two statistically significant changes were identified in the pregnant uterus: (1) a periimplantation surge between day 3 (0.24 nmoVmg protein) and day 5 (0.59 nmoYmg protein) of gestation (plug day 0; implantation day 4); and (2) an early postimplantation decline between day 6 (0.54 nmollmg protein) and day 7 (0.10 nmollmg protein). The periimplantation adenosine surge coincided with uterine expression of 5'-NT, an enzyme which catalyzes the irreversible dephosphorylation of 5'-AMP to adenosine. 5'-NT expression was shown by Northern blot analysis to peak in the embryo-decidual unit on day 5 of gestation and then to decline through day 9; transcripts remained elevated in the placenta between day 9 and day 13 (the latest day examined in this study). By use of specific enzyme histochemistry, most 5'-NT activity was localized to the primary decidual :zone on day 5. This expression subsequently declined during regression of the primary decidua; however, 5'-NT appeared on giant trophoblast ((days 7-13) and the metrial gland (days 11-13).Other purine catabolic enzymes degrading AMP (adenylate deaminase) or generating adenosine (S-adenosylhomocysteine hydrolase) were not detected in the embryo-decidual unit suggesting that the net flux of utero-placental AMP catabolism proceeds with adenosine as an intermediate, this being the major pathway of adenosine formation.The sharp drop in adenosine levels between day 6 and day 7 coincided with a rise in the activity and mRNA expression of ADA, an enzyme which catalyzes the irreversible deamination of adenosine to inosine. ADA was previously localized to the secondary decidual zone (days 6 1 l), secondary giant cells (days 7-13), and spongiotrophoblasts (days 8-13) in the mouse (Knudsen et al., 1991). Results of developmental Northern blot analysis demonstrated a direct correlation of relative 5'-NT/ADA mRNA band intensity to adenosine content between day 4 and day 9 of gestation, suggesting that the local availability of adenosine in the antimesometrium is dependent upon the distribution of these enzymatic activities. Purine nucleoside phosphorylase and xanthine oxidase, which are two catabolic enzymes acting subsequent to 5'-NT and ADA in the sequential degradation of AMP to xanthine, remained low and constant in the tissues examined suggesting that the catabolic pathway is geared toward regulation of adenosine le...

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Section: Transmural Asymmetry Of Adenosine Concentration Across the Amentioning

confidence: 99%

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Blackburn

Gao

Airhart

et al. 1992

Developmental Dynamics

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“…Vascular cells release nucleotides when exposed to stimuli such as ischemia, hypoxia, and chemical or mechanical stress (3,4). It also is becoming apparent that extracellular nucleotides can promote the development of a variety of pathologies including disorders of the immune system, and neurodegenerative and vascular diseases (1).…”

mentioning

confidence: 99%

The P2Y2 Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells

Seye

Jain

et al. 2003

Journal of Biological Chemistry

106

114

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Extracellular nucleotides cause a wide range of cellular responses and appear to play a role in the regulation of many vascular functions (1, 2). Vascular cells release nucleotides when exposed to stimuli such as ischemia, hypoxia, and chemical or mechanical stress (3, 4). It also is becoming apparent that extracellular nucleotides can promote the development of a variety of pathologies including disorders of the immune system, and neurodegenerative and vascular diseases (1). Indeed, ATP or UTP induces proliferation and migration of vascular smooth muscle cells, two processes involved in the development of intimal lesions found in atherosclerosis and post-angioplasty restenosis. The biological effects of extracellular nucleotides are mediated through activation of P1 and P2 purinergic receptors. P1 receptors are responsive to adenosine, whereas P2 receptors are activated by a variety of nucleotides including ATP and UTP (5, 6). The P2 receptors are subdivided into two distinct categories, the metabotropic Gprotein-coupled (P2Y) receptors and the ionotropic ligandgated channel (P2X) receptors (6, 7). Vascular cells have been shown to express metabotropic P2Y and ionotropic P2X receptors (5, 8). It has been reported that P2Y 2 receptors are upregulated in cells of rat intimal lesions following balloon angioplasty (9). Our recent studies showed that placement of a silicone collar around the rabbit carotid artery promoted upregulation of P2Y 2 receptors in vascular smooth muscle cells and endothelium (10). Subsequently, local infusion of UTP was shown to stimulate intimal hyperplasia and increase intimal monocyte infiltration (10), suggesting a role for P2Y 2 receptors in the recruitment of blood monocytes leading to inflammation in atherosclerosis.Monocyte recruitment into the vessel wall is a complex process that includes cell rolling, firm attachment, and directed migration. It is now becoming evident that adhesion molecules such as VCAM-1 play an important role in leukocyte adherence to vascular endothelial cells (11,12). VCAM-1 expression is induced or up-regulated by proinflammatory cytokines such as TNF-␣ 1 and interleukin 1-␤ on cellular components of the arterial wall including endothelial cells, smooth muscle cells, and fibroblasts (13-15). ATP and UTP have been shown to induce cell-cell adhesion in a monocyte/macrophage lineage and neutrophil adherence to an endothelial cell monolayer (16,17), raising the possibility that released ATP and UTP could induce endothelial cell activation by an autocrine/paracrine mechanism to regulate leukocyte adherence.

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“…A concerted effort to identify possible natural substrates seems justified. Perhaps chondrocytes may become "leaky" under certain physiologic or pathologic conditions, much as endothelial cells or platelets release ATP in response to trauma or enzymatic insult (27). Leaked substrate could be converted to PPi which might accumulate in areas relatively deficient in pyrophosphatase, as discussed by Howell et a1 (24).…”

Section: Discussionmentioning

confidence: 99%

Cartilage nucleoside triphosphate pyrophosphohydrolase. II. role in extracellular pyrophosphate generation and nucleotide metabolism

Ryan

Wortmann

Karas

et al. 1985

Arthritis & Rheumatism

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Extracellular generation of inorganic pyrophosphate (PPi) in cartilage organ culture is markedly augmented by ATP. ATP, not an ATP metabolite (ADP, AMP, adenosine), is necessary for this augmentation. Excess PPi production is effectively blocked by known inhibitors of nucleoside triphosphate (NTP) pyrophosphohydrolase (EDTA, EGTA, dithiothreitol). Excess 32P-PPi is generated directly from g2P-ATP by cartilage, as substrate and product have similar specific activities. These findings strongly favor ecto-NTP pyrophosphohydrolase as the source of extracellular PPi generation in the presence of NTP. Additionally, active nucleotide and nucleoside catabolism is demonstrated in these cartilage organ cultures.Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is defined by the presence of CPPD crystals in articular fluid or tissues. These crystals often cause an inflammatory arthritis (pseudo-

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Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides

Cited by 385 publications

References 18 publications

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

Adenosine levels in the postimplantation mouse uterus: Quantitation by HPLC‐fluorometric detection and spatiotemporal regulation by 5′‐nucleotidase and adenosine deaminase

The P2Y2 Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells

Cartilage nucleoside triphosphate pyrophosphohydrolase. II. role in extracellular pyrophosphate generation and nucleotide metabolism

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