[125I]Aminobenzyladenosine, a new radioligand with improved specific binding to adenosine receptors in heart.

Linden, Joel; Patel, Amrat; Sadek, Samy

doi:10.1161/01.res.56.2.279

Cited by 72 publications

(34 citation statements)

References 15 publications

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“…Inhibitory constant values for different compounds were derived from IC50 values as described (13). Data from triplicate experiments are tabulated as means Ϯ SE.…”

Section: Methodsmentioning

confidence: 99%

Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Peirce

Skalak

Rieger³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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Activation of A2A adenosine receptors (A2A-AR) by ATL-146e (formerly DWH-146e) prevents inflammatory cell activation and adhesion. Recurrent ischemia-reperfusion (I/R) of the skin results in pressure ulcer formation, a major clinical problem. ATL-146e was evaluated in a novel reproducible rat model of pressure ulcer. A 9-cm2 region of dorsal rat skin was cyclically compressed at 50 mmHg using a surgically implanted metal plate and an overlying magnet to generate reproducible tissue necrosis. Osmotic minipumps were implanted into 24 rats divided into four equal groups to infuse vehicle (control), ATL-146e (0.004 μg · kg−1 · min−1), ATL-146e plus an equimolar concentration of A2A antagonist, ZM-241385, or ZM-241385 alone. Each group received 10 I/R cycles. In non-I/R-treated skin, ATL-146e has no effect on blood flow. I/R-treated skin of the ATL-146e group compared with the vehicle group had 65% less necrotic area, 31% less inhibition of average skin blood flow, and fewer extravasated leukocytes (23 ± 3 vs. 49 ± 6 per 500 μm2). These data suggest that ATL-146e, acting via an A2A-AR, reduces leukocyte infiltration and is a potent prophylactic for I/R injury in skin.

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“…Inhibitory constant values for different compounds were derived from IC50 values as described (13). Data from triplicate experiments are tabulated as means Ϯ SE.…”

Section: Methodsmentioning

confidence: 99%

Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Peirce

Skalak

Rieger³

et al. 2001

American Journal of Physiology-Heart and Circulatory Physiology

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“…The number of high-affinity agonist binding sites, a measure of G-protein-coupled receptors, was determined using the agonist radioligand 125 I-ABA (28 …”

Section: Methodsmentioning

confidence: 99%

Transgenic A ₁ adenosine receptor overexpression increases myocardial resistance to ischemia

Matherne

Linden

Byford

et al. 1997

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

150

176

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Activation of myocardial A 1 adenosine receptors (A 1 AR) protects the heart from ischemic injury. In this study transgenic mice were created using the cardiac-specific ␣-myosin heavy chain promoter and rat A 1 AR cDNA. Heart membranes from two transgene positive lines displayed Ϸ1,000-fold overexpression of A 1 AR (6,574 ؎ 965 and 10,691 ؎ 1,002 fmol per mg of protein vs. 8 ؎ 5 fmol per mg of protein in control hearts). Compared with control hearts, transgenic Langendorff-perfused hearts had a significantly lower intrinsic heart rate (248 beats per min vs. 318 beats per min, P < 0.05), lower developed tension (1.2 g vs. 1.6 g, P < 0.05), and similar coronary resistance. The difference in developed tension was eliminated by pacing. Injury of control hearts during global ischemia, indexed by time-to-ischemic contracture, was accelerated by blocking adenosine receptors with 50 M 8-(p-sulfophenyl) theophylline but was unaffected by addition of 20 nM N 6 -cyclopentyladenosine, an A 1 AR agonist. Thus A 1 ARs in ischemic myocardium are presumably saturated by endogenous adenosine. Overexpressing myocardial A 1 ARs increased time-to-ischemic contracture and improved functional recovery during reperfusion. The data indicate that A 1 AR activation by endogenous adenosine affords protection during ischemia, but that the response is limited by A 1 AR number in murine myocardium. Overexpression of A 1 AR affords additional protection. These data support the concept that genetic manipulation of A 1 AR expression may improve myocardial tolerance to ischemia.

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“…For binding assays, membranes were thawed and diluted 5-to 10-fold with HE to a final membrane protein concentration of approximately 1 mg/ml. Saturation binding assays for rat adenosine receptors were performed, respectively, with 125 I-ABA for A 1 and A 3 ARs (Linden et al, 1985;Salvatore et al, 1993), 125 I-ZM241385 for A 2A AR (Sullivan et al, 1999), and [ 125 I]3-(4-amino-3-iodobenzyl)-8-oxyacetate-1-propylxanthine for A 2B AR . Nonspecific binding was defined using 100 M 5Ј-N-ethylcarboxamidoadenosine.…”

Section: Abbreviationsmentioning

confidence: 99%

A₃Adenosine Receptor Activation Triggers Phosphorylation of Protein Kinase B and Protects Rat Basophilic Leukemia 2H3 Mast Cells from Apoptosis

Gao

Li²,

Day³

et al. 2001

Mol Pharmacol

124

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Adenosine accumulates to high levels in inflamed or ischemic tissues and activates A 3 adenosine receptors (ARs) on mast cells to trigger degranulation. Here we show that stimulation of rat basophilic leukemia (RBL)-2H3 mast-like cells with the A 3 AR agonists N 6 -(3-iodo)benzyl-5Ј-N-methylcarboxamidodoadenosine (IB-MECA; 10 nM) or inosine (10 M) stimulates phosphorylation of protein kinase B (Akt). IB-MECA (1 M) also causes a Ͼ50% reduction in apoptosis caused by exposure of RBL-2H3 cells to UV light. Akt phosphorylation is not stimulated by 100 nM N 6 -cyclopentyladenosine (A 1 -selective) or CGS21680 (A 2A -selective) and is absent in cells pretreated with wortmannin or pertussis toxin. The K I values of the AR antagonists BW-1433 and 8-sulfophenyltheophylline (8-SPT) were determined in radioligand binding assays for all four subtypes of rat ARs: BW-1433 (A 1 , 5.8 Ϯ 1.0 nM; A 2A , 240 Ϯ 37; A 2B , 30 Ϯ 10; A 3 , 12,300 Ϯ 3,700); 8-SPT (A 1 , 3.2 Ϯ 1.2 M; A 2A , 57 Ϯ 4; A 2B , 2.2 Ϯ 0.8; A 3 , Ͼ100). BW-1433 and the A 3 -slective antagonist MRS1523 (5 M), but not 8-SPT (100 M), block IB-MECA-induced protection from apoptosis, confirming the A 3 AR as the mediator of the antiapoptotic response. The data suggest that adenosine and inosine activate Gi-coupled A 3 ARs to protect mast cells from apoptosis by a pathway involving the ␤␥ subunits of Gi, phosphatidylinositol 3-kinase ␤, and Akt. We speculate that activation of A 3 ARs on mast cells or other cells that express A 3 ARs (e.g., eosinophils) may facilitate their survival and accumulation in inflamed tissues.Activation of the serine/threonine kinase, Akt, also called protein kinase B (PKB) inhibits programmed cell death Kandel et al., 1999;Stambolic et al., 1999). Phosphoinositides generated by activated phosphatidylinositol 3-kinases (PI3Ks) bind to the plextrin homology domain on Akt and stimulate its translocation to the plasma membrane, where it is phosphorylated on both Ser473 and Thr308 and activated by phosphoinositide-dependent kinase-1 . PI3Ks can be activated by tyrosine kinase growth factor receptors, or in some cells by activation of G protein-coupled receptors. Activation of PI3K via heterotrimeric G proteins occurs selectively in cells that express PI3K␤ (Murga et al., 2000). Hence, it is possible that Akt is involved in the regulation of apoptosis that has been noted in astrocytes and cardiomyocytes by G protein-coupled A 3 ARs (Jacobson, 1998). The A 3 AR is known to regulate the degranulation of rodent perivascular mast cells and RBL-2H3 mast-like cultured cells (Ramkumar et al., 1993). Activation of mast cell A 3 ARs increases mast cell degranulation to release histamine and other allergic mediators. This prompted us to determine in this study whether A 3 AR activation protects RBL-2H3 mast cells from apoptosis. We show that IB-MECA, Cl-IB-MECA, and inosine signal via A 3 ARs to stimulate phosphorylation of Akt and to reduce RBL-2H3 cell apoptosis induced by UV light. Experimental ProceduresMaterials. CPA, 5Ј-N-ethylcarboxamidoad...

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[125I]Aminobenzyladenosine, a new radioligand with improved specific binding to adenosine receptors in heart.

Cited by 72 publications

References 15 publications

Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Transgenic A ₁ adenosine receptor overexpression increases myocardial resistance to ischemia

A₃Adenosine Receptor Activation Triggers Phosphorylation of Protein Kinase B and Protects Rat Basophilic Leukemia 2H3 Mast Cells from Apoptosis

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[125I]Aminobenzyladenosine, a new radioligand with improved specific binding to adenosine receptors in heart.

Cited by 72 publications

References 15 publications

Selective A2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Selective A2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Transgenic A 1 adenosine receptor overexpression increases myocardial resistance to ischemia

A3Adenosine Receptor Activation Triggers Phosphorylation of Protein Kinase B and Protects Rat Basophilic Leukemia 2H3 Mast Cells from Apoptosis

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Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Selective A_2Aadenosine receptor activation reduces skin pressure ulcer formation and inflammation

Transgenic A ₁ adenosine receptor overexpression increases myocardial resistance to ischemia

A₃Adenosine Receptor Activation Triggers Phosphorylation of Protein Kinase B and Protects Rat Basophilic Leukemia 2H3 Mast Cells from Apoptosis