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Adenosine A_2A and A₃ Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

ABSTRACT: Diabetic nephropathy (DN) and hypertension are prime causes for end-stage renal disease (ESRD) that often coexist in patients, but are seldom studied in combination. Kidney adenosine levels are markedly increased in diabetes, and the expression and function of renal adenosine receptors are altered in experimental diabetes. The aim of this work is to explore the impact of endogenous and exogenous adenosine on the expression/distribution profile of its receptors along the nephron of hypertensive rats with experimentally-induced diabetes. Using spontaneously hypertensive (SHR) rats rendered diabetic with streptozotocin (STZ), we show that treatment of SHR-STZ rats with an agonist of adenosine receptors increases A_2A immunoreactivity in superficial glomeruli (SG), proximal tubule (PCT), and distal tubule (DCT). Differently, treatment of SHR-STZ rats with a xanthinic antagonist of adenosine receptors decreases adenosine A₃ immunoreactivity in SG, PCT, DCT, and collecting duct. There is no difference in the immunoreactivity against the adenosine A₁ and A_2B receptors between the experimental groups. The agonist of adenosine receptors ameliorates renal fibrosis, probably via A_2A receptors, while the antagonist exacerbates it, most likely due to tonic activation of A₃ receptors. The reduction in adenosine A₃ immunoreactivity might be due to receptor downregulation in response to prolonged activation. Altogether, these results suggest an opposite regulation exerted by endogenous and exogenous adenosine upon the expression of its A_2A and A₃ receptors along the nephron of hypertensive diabetic rats, which has a functional impact and should be taken into account when considering novel therapeutic targets for hypertensive-diabetic nephropathy.

SUBMITTER: Patinha D

PROVIDER: S-EPMC7700226 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Adenosine A<sub>2A</sub> and A<sub>3</sub> Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

Patinha Daniela D Abreu Carla C Carvalho Carla C Cunha Olga Mariana OM Mota Mariana M Afonso Joana J Sousa Teresa T Albino-Teixeira António A Diniz Carmen C Morato Manuela M

Biomedicines 20201123 11

Diabetic nephropathy (DN) and hypertension are prime causes for end-stage renal disease (ESRD) that often coexist in patients, but are seldom studied in combination. Kidney adenosine levels are markedly increased in diabetes, and the expression and function of renal adenosine receptors are altered in experimental diabetes. The aim of this work is to explore the impact of endogenous and exogenous adenosine on the expression/distribution profile of its receptors along the nephron of hypertensive r ...[more]

PMID: 33238361

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Dataset Information

Adenosine A_2A and A₃ Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

Publications

Adenosine A<sub>2A</sub> and A<sub>3</sub> Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

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Dataset Information

Adenosine A2A and A3 Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

Publications

Adenosine A<sub>2A</sub> and A<sub>3</sub> Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Adenosine A_2A and A₃ Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.