Identification of Adenosine A2 Receptor-cAMP System in Human Aortic Endothelial Cells

Iwamoto, Tamio; Umemura, Satoshi; Toya, Yoshiyuki; Uchibori, Takehiro; Kogi, Kentaro; Takagi, Nobuhiro; Ishii, Masao

doi:10.1006/bbrc.1994.1314

Cited by 94 publications

(59 citation statements)

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“…CXCL8 is known as a potent stem cell-mobilizing agent (Laterveer et al, 1995), and it also increases the proliferation of hematopoietic progenitor cells in vitro (Hermouet et al, 2000). Human aortic endothelial cells (HAECs) express the A 2b receptor (Iwamoto et al, 1994), and we confirmed A 2b expression by RT-PCR (not depicted). We treated HAECs with BAY 60-6583, which increased CXCL8 protein production Adenosine regulates HSC formation via cAMP-PKA A 2b receptor is commonly coupled to adenylyl cyclase via G protein subunit Gs and increases intracellular cAMP that activates PKA (Fredholm, 2007).…”

Section: Adenosine Regulates the Formation Of Hscssupporting

confidence: 61%

Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

Jing¹,

Tamplin²,

Chen³

et al. 2015

J Cell Biol

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Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-tohematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A 2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1 + /cmyb + HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A 2b adenosine receptor disrupted scl + hemogenic vascular endothelium and the subsequent EHT process. A 2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.

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Section: Adenosine Regulates the Formation Of Hscssupporting

confidence: 61%

Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

Jing¹,

Tamplin²,

Chen³

et al. 2015

J Cell Biol

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“…These receptors are classified according to use of pertussis toxin-sensitive pathways (A 1 and A 3 ) or adenylate cyclase activation pathways (A 2A and A 2B ) (5). Endothelial cells of many origins express constitutive adenosine receptors (5), primarily of the A 2A and A 2B subtypes (27)(28)(29)(30). The present studies define a transcriptional pathway mediated by adenosine receptor activation, including but not limited to CD73.…”

Section: Discussionmentioning

confidence: 93%

Regulation of Endothelial CD73 by Adenosine: Paracrine Pathway for Enhanced Endothelial Barrier Function

Narravula

Lennon

Mueller

et al. 2000

The Journal of Immunology

109

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During episodes of inflammation, multiple cell types release adenine nucleotides in the form of ATP, ADP, 5′-AMP, and adenosine. In particular, following activation, polymorphonuclear leukocytes release larger quantities of 5′-AMP. Extracellular 5′-AMP is metabolized to adenosine by surface-expressed 5′-ectonucleotidase (CD73). Adenosine liberated by this process activates surface adenosine A2B receptors, results in endothelial junctional reorganization, and promotes barrier function. We hypothesized that adenosine signaling to endothelia provides a paracrine loop for regulated expression of CD73 and enhanced endothelial barrier function. Using an in vitro microvascular endothelial model, we investigated the influence of 5′-AMP; adenosine; and adenosine analogues on CD73 transcription, surface expression, and function. Initial experiments revealed that adenosine and adenosine analogues induce CD73 mRNA (RT-PCR), surface expression (immunoprecipitation of surface biotinylated CD73), and function (HPLC analysis of etheno-AMP conversion to ethenoadenosine) in a time- and concentration-dependent fashion. Subsequent studies revealed that similar exposure conditions increase surface protein through transcriptional induction of CD73. Analysis of DNA-binding activity by EMSA identified a functional role for CD73 cAMP response element and, moreover, indicated that multiple cAMP agonists induce transcriptional activation of functional CD73. Induced CD73 functioned to enhance 5′-AMP-mediated promotion of endothelial barrier (measured as a paracellular flux of 70-kDa FITC-labeled tracer). These results provide an example of transcriptional induction of enzyme (CD73) by enzymatic product (adenosine) and define a paracrine pathway for the regulated expression of vascular endothelial CD73 and barrier function.

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“…The adenosine receptor on guinea pig microvascular coronary endothelial cells was identified as the A 2A subtype (Schiele and Schwabe, 1994). Both A 2A and A 2B receptors were described on human aortic endothelial cells (Iwamoto et al, 1994). A 2A and A 2B receptors were also shown to be present on porcine coronary artery endothelial cells .…”

Section: Purinergic Signaling and Blood Vesselsmentioning

confidence: 90%