scholarly journals Effects of the adenosine A1 receptor inhibitor FK 838 on proximal tubular fluid output in rats

2004 ◽  
Vol 19 (5) ◽  
pp. 1077-1082 ◽  
Author(s):  
M. Bak ◽  
K. Thomsen
Keyword(s):  
Adenosine A1 Receptor ◽  
Adenosine A1 ◽  
Proximal Tubular ◽  
A1 Receptor ◽  
Receptor Inhibitor

scholarly journals Adenosine A1 Receptor Deficiency Aggravates Extracellular Matrix Accumulation in Diabetic Nephropathy through Disturbance of Peritubular Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Dongli Tian ◽  
Jiaying Li ◽  
Linfeng Zou ◽  
Min Lin ◽  
Xiaoxiao Shi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Immunohistochemical Staining ◽  
Adenosine A1 Receptor ◽  
Pronounced Increase ◽  
Matrix Deposition ◽  
Adenosine A1 ◽  
Proximal Tubular ◽  
A1 Receptor

Background. We previously observed that adenosine A1 receptor (A1AR) had a protective role in proximal tubular megalin loss associated with albuminuria in diabetic nephropathy (DN). In this study, we aimed to explore the role of A1AR in the fibrosis progression of DN. Methods. We collected DN patients’ samples and established a streptozotocin-induced diabetes model in wild-type (WT) and A1AR-deficient (A1AR-/-) mice. The location and expression of CD34, PDGFRβ, and A1AR were detected in kidney tissue samples from DN patients by immunofluorescent and immunohistochemical staining. We also analyzed the expression of TGFβ, collagen (I, III, and IV), α-SMA, and PDGFRβ using immunohistochemistry in WT and A1AR-/- mice. CD34 and podoplanin expression were analyzed by Western blotting and immunohistochemical staining in mice, respectively. Human renal proximal tubular epithelial cells (HK2) were cultured in medium containing high glucose and A1AR agonist as well as antagonist. Results. In DN patients, the expression of PDGFRβ was higher with the loss of CD34. The location of PDGFRβ and TGFβ was near to each other. The A1AR, which was colocalized with CD34 partly, was also upregulated in DN patients. In WT-DN mice, obvious albuminuria and renal pathological leisure were observed. In A1AR-/- DN mice, more severe renal tubular interstitial fibrosis and more extracellular matrix deposition were observed, with lower CD34 expression and pronounced increase of PDGFRβ. In HK2 cells, high glucose stimulated the epithelial-mesenchymal transition (EMT) process, which was inhibited by A1AR agonist. Conclusion. A1AR played a critical role in protecting the tubulointerstitial fibrosis process in DN by regulation of the peritubular microenvironment.

Adenosine A1 Receptor Antagonist Up-regulates Casp3 and Stimulates Apoptosis Rate in Breast Cancer Cell Line T47D

2020 ◽  
Vol 9 (1) ◽  
pp. 14-20
Author(s):  
Mohammad Zamani Rarani ◽  
Fahimeh Zamani Rarani ◽  
Ali Valiani ◽  
Zeinolabedin Shrifian Dastjerdi ◽  
Elias Kargar Abargouei ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell Line ◽  
P53 Gene ◽  
T47d Cell ◽  
Adenosine A1 Receptor ◽  
T47d Cells ◽  
Apoptosis Rate ◽  
Adenosine A1 ◽  
T47d Cell Line ◽  
A1 Receptor

Background: Adenosine receptor family, especially A1 type is-overexpressed in breast-derived tumor cells and the P53 gene is mutant in some of these cells while the casps gene is of wild type as well. The aim of this study was to evaluate the effect of the A1 receptor function on cell programmed death or proliferation, as well as the relationship between this receptor stimulation/inhibition and caspase 3 (casp3) expression in T47D cell line that has a mutant and non-functional P53 gene. Materials and Methods: The expression of casps3 was measured by real-time polymerase chain reaction and then flow cytometery and MTT assay were used to assess the apoptotic and proliferation cell rate after the treatment of T47D cells with specific agonist N6-cyclopentyladenosine (CPA) and antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) of this receptor 24, 48, and 72 hours after treatment. Result: Our results indicated that DPCPX significantly induces apoptosis in T47D cells and the rate of survival cell after the reduction of this treatment, especially 72 hours after treatment. Finally, the expression of casp3 was up-regulated by DPCPX treatment, especially in 72 hours while CPA treatment had opposite results (P>0.05). Conclusion: In general, DPCPX could up-regulate casp3 gene expression and subsequently increase the apoptosis rate in T47D cells with casp3 expression without the P53 gene interference. Therefore, adenosine A1 receptor antagonists may be introduced as anti-cancer agents.

scholarly journals Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1112
Author(s):  
Lingyu Ruan ◽  
Guanghui Li ◽  
Wenlong Zhao ◽  
Huihui Meng ◽  
Qi Zheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glutamate Release ◽  
Chinese Herb ◽  
Adenosine A1 Receptor ◽  
Polygonum Multiflorum ◽  
Stroke Treatment ◽  
Cardiovascular Side Effects ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Underlying Mechanisms

Ischemic stroke is the main cause of death/disability, posing a great menace to human health. Though efforts to search for therapeutic drugs are ongoing, few of them have succeeded. Adenosine A1 receptor (A1R) activation could ameliorate ischemic injury, representing a very tempting target for stroke treatment. Tetrahydroxy stilbene glycoside (TSG), a potent antioxidant from the well-known Chinese herb Polygonum multiflorum Thunb., has been reported to have notable neuroprotective activities but the underlying mechanisms are elusive. This study investigated the mechanism of TSG focusing on A1R. TSG markedly decreased mortality, neurological deficit score, cerebral infarct size and brain water content of MCAO rats, and ameliorated the disorders in purine metabolism, energy metabolism and antioxidative defense system. TSG helped the survival of SH-SY5Y cells in OGD/R by alleviating oxidative stress and glutamate release, and by maintaining calcium homeostasis. TSG effects were abolished by A1R antagonist DPCPX. Docking and binding assays confirmed the binding of TSG with A1R. In addition, TSG upregulated the A1R level lowered by MCAO and OGD/R. The downstream signals of A1R activation, ERK1/2, HIF-1α and NF-κB contributed to the neuroprotection of TSG. Moreover, void of “well-known” cardiovascular side effects of classical A1R agonists, TSG showcased its great potential for stroke treatment.

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