Effects of selective adenosine A2 receptor agonist on renal function in dogs

The effects of adenosine in the nonischemic heart have been shown to be mediated via its binding to extracellular adenosine A1 and A2 receptors located predominantly on myocytes and endothelial cells, respectively. We tested the hypothesis that the beneficial effect of adenosine on postischemic myocardial function is mediated via an adenosine A1 receptor mechanism. Isolated rat hearts perfused at constant pressure (85 cmH2O) were subjected to 30 min of global no-flow ischemia (37 degrees C) and 45 min of reperfusion. Hearts treated with adenosine (100 microM) and the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA; 0.25 microM) recovered 72 +/- 4 and 70 +/- 4% of preischemic left ventricular developed pressures (LVDP), respectively, after 45 min of reperfusion compared with untreated hearts (54 +/- 3% of preischemic LVDP). Adenosine and CHA hearts exhibited greater myocardial ATP contents than control hearts after 10 min of ischemia, but there were no differences in tissue ATP levels after 30 min of ischemia. In contrast, hearts treated with the adenosine A2 receptor agonist phenylaminoadenosine (0.25 microM) failed to demonstrate improved postischemic function (52 +/- 5%). The addition of the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the cardioprotective effect of adenosine (57 +/- 4%). These results suggest that adenosine enhances postischemic myocardial function via an A1 receptor mechanism.

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Effects of short IV infusions of DT-009, a novel adenosine (A?) receptor agonist, on renal function in healthy subjects

Clinical Pharmacology & Therapeutics ◽

10.1016/j.clpt.2004.12.112 ◽

2005 ◽

Vol 77 (2) ◽

pp. P58-P58

Author(s):

J VENITZ ◽

D SICA ◽

R TOWNSEND ◽

M DESSIMOZ

Keyword(s):

Renal Function ◽

Healthy Subjects ◽

Receptor Agonist

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Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels

European Journal of Pharmacology ◽

10.1016/0014-2999(92)90682-t ◽

1992 ◽

Vol 213 (2) ◽

pp. 199-204 ◽

Cited By ~ 23

Author(s):

Fumiya Yoneyama ◽

Hiroaki Yamada ◽

Keisuke Satoh ◽

Norio Taira

Keyword(s):

Receptor Agonist ◽

K Channels ◽

Adenosine A2 Receptor

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GLP-1 receptor agonist ameliorates obesity-induced chronic kidney injury via restoring renal lipid and energy metabolism homeostasis: revealed by metabolomics

10.1101/194654 ◽

2017 ◽

Author(s):

Chengshi Wang ◽

Ling Li ◽

Shuyun Liu ◽

Guangneng Liao ◽

Younan Chen ◽

...

Keyword(s):

Renal Function ◽

Energy Metabolism ◽

High Fat Diet ◽

Receptor Agonist ◽

Kidney Diseases ◽

Kidney Injury ◽

Direct Role ◽

Chronic Kidney Injury ◽

Metabolomic Data

AbstractIncreasing evidence indicate that obesity is highly associated with chronic kidney disease (CKD).GLP-1 receptor (GLP-1R) agonist has shown benefits on kidney diseases, but its direct role on kidney metabolism in obesity is still not clear. This study aims to investigate the protection and metabolic modulation role of liraglutide (Lira) on kidney of obesity. Rats were induced obese by high-fat diet (HFD), and renal function and metabolism changes were evaluated by metabolomic, biological and histological methods. HFD rats exhibited metabolic disorders including elevated body weight, hyperlipidemia and impaired glucose tolerance, and remarkable renal injuries including declined renal function and inflammatory/fibrotic changes, whereas Lira significantly ameliorated these adverse effects in HFD rats. Metabolomic data showed that Lira reduced renal lipids including fatty acid residues, cholesterol, phospholipids and triglycerides, and improved mitochondria metabolites such as succinate, citrate, taurine, fumarate and NAD+ in the kidney of HDF rats. Furthermore, we revealed that Lira inhibited renal lipid accumulation by coordinating lipogenic and lipolytic signals, and rescued renal mitochondria function via Sirt1/AMPK/PGC1α pathways in HDF rats. This study suggested that Lira alleviated HFD-induced kidney injury via directly restoring renal lipid and energy metabolism, and GLP-1 receptor agonist is a promising therapy for obesity-associated CKD.

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