PP003. Antagonism in A2A and A2B adenosine receptor on fetal endothelium proliferation involves a nitric oxide-depended intracellular pathway in early and late-onset pre-eclampsia

We previously demonstrated that nitric oxide (NO) contributes to compensatory vasodilation in the contracting human forearm subjected to acute hypoperfusion. We examined the potential role of an adenosine-NO interaction to this response in 17 male subjects (25 ± 2 yr). In separate protocols subjects performed rhythmic forearm exercise (20% of maximum) while hypoperfusion was evoked by balloon inflation in the brachial artery above the elbow. Each trial included exercise before inflation, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound) and local [brachial artery catheter pressure (BAP)] and systemic [mean arterial pressure (MAP); Finometer] arterial pressure were measured. In protocol 1 ( n = 10), exercise was repeated during nitric oxide synthase inhibition [ NG-monomethyl-l-arginine (l-NMMA)] alone and during l-NMMA-aminophylline (adenosine receptor blockade) administration. In protocol 2, exercise was repeated during aminophylline alone and during aminophylline-l-NMMA. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1) was calculated from blood flow (ml/min) and BAP (mmHg). Percent recovery in FVC during inflation was calculated as (steady-state inflation + exercise value − nadir)/[steady-state exercise (control) value − nadir]. In protocol 1, percent recovery in FVC was 108 ± 8% during the control (no drug) trial. Percent recovery in FVC was attenuated with inhibition of NO formation alone (78 ± 9%; P < 0.01 vs. control) and was attenuated further with combined inhibition of NO and adenosine (58 ± 9%; P < 0.01 vs. l-NMMA). In protocol 2, percent recovery was reduced with adenosine receptor blockade (74 ± 11% vs. 113 ± 6%, P < 0.01) compared with control drug trials. Percent recovery in FVC was attenuated further with combined inhibition of adenosine and NO (48 ± 11%; P < 0.05 vs. aminophylline). Our data indicate that adenosine contributes to compensatory vasodilation in an NO-independent manner during exercise with acute hypoperfusion.

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The Regulation of p27Kip-1and Bcl2 Expression Is Involved in the Decrease of Osteoclast Proliferation by A2B Adenosine Receptor Stimulation

Biomedical Science Letters ◽

10.15616/bsl.2017.23.4.327 ◽

2017 ◽

Vol 23 (4) ◽

pp. 327-332

Author(s):

Hong Sung Kim ◽

Na Kyung Lee

Keyword(s):

Adenosine Receptor ◽

Receptor Stimulation ◽

A2b Adenosine Receptor ◽

Bcl2 Expression

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Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury

The Journal of Immunology ◽

10.4049/jimmunol.1002907 ◽

2010 ◽

Vol 186 (2) ◽

pp. 1097-1106 ◽

Cited By ~ 78

Author(s):

Yang Zhou ◽

Daniel J. Schneider ◽

Eva Morschl ◽

Ling Song ◽

Mesias Pedroza ◽

...

Keyword(s):

Lung Injury ◽

Adenosine Receptor ◽

A2b Adenosine Receptor

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Abstract 294: The A2b Adenosine Receptor and Newly Identified Opposing Effects of cAMP on Insulin Secretion

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a294 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Hillary A Johnston-Cox ◽

Barbara Corkey ◽

Katya Ravid

Keyword(s):

Insulin Secretion ◽

Adenosine Receptor ◽

Underlying Mechanism ◽

Short Exposure ◽

A2b Adenosine Receptor ◽

Downstream Effects ◽

Glucose Challenge ◽

Short And Long Term ◽

Glucose Stimulated Insulin Secretion ◽

Opposing Effects

The A2b adenosine receptor (A2bAR) is a G-protein coupled receptor that, upon binding of adenosine, activates adenylyl cyclase and mediates downstream effects through secondary messengers, including cyclic 3’5’ AMP (cAMP) and Ca ++ . We have previously demonstrated that A2bAR knockout (KO) KO mice, post-high fat diet (HFD) develop a type 2 diabetic (T2D) phenotype, evidenced by elevated plasma insulin and glucose. Pancreatic islets from A2bAR KO mice demonstrated insulin hypersecretion post-4 weeks HFD, and high glucose challenge. To further understand the underlying mechanism, we focused on the contribution of the pancreatic A2bAR to this phenomnena. cAMP has been demonstrated to be a significant amplifier of glucose-stimulated insulin secretion. Through the use of A2bAR KO islets and diet-induced stress, we identified a new dual role for cAMP in mediating insulin secretion, dependent on cAMP level and duration. Short exposure to elevated cAMP indeed causes insulin hypersecretion. cAMP has, however, also a downregulating effect on the expression of GLUT2 mRNA and protein, which has the potential to inhibit insulin secretion. Thus, A2bAR short and long-term signaling in the pancreas play an important role in insulin homeostasis.

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Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/107424849600100303 ◽

1996 ◽

Vol 1 (3) ◽

pp. 203-209 ◽

Cited By ~ 1

Author(s):

Roberto Pedrinelli

Keyword(s):

Nitric Oxide ◽

Sodium Nitroprusside ◽

Adenosine Receptor ◽

Guanosine Monophosphate ◽

Muscarinic Agonist ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Nitric Oxide Synthase Inhibitor ◽

Adenosine Receptor Agonist ◽

Synthase Inhibitor

Background To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. Methods and Results Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A2-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. Conclusion Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A2 adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

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