Portal de investigação
Adenosine A2A and A3 Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- Patinha, D
- Abreu, C
- Carvalho, C
- Cunha, OM
- Mota, M
- Afonso, J
- Albino-Teixeira, A
- Diniz, C
- Morato, M
Unidades de investigação
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 A(3) immunoreactivity in SG, PCT, DCT, and collecting duct. There is no difference in the immunoreactivity against the adenosine A(1) 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 A(3) receptors. The reduction in adenosine A(3) 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 A(3) 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.
Dados da publicação
- ISSN/ISSNe:
- 2227-9059, 2227-9059
- Tipo:
- Article
- Páginas:
- 1-19
- Link para outro recurso:
- www.scopus.com
Biomedicines MDPI AG
Citações Recebidas na Web of Science: 8
Citações Recebidas na Scopus: 11
Documentos
- Não há documentos
Filiações
Keywords
- diabetes; hypertension; diabetic complications; diabetic nephropathy; adenosine receptors
Financiamento
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Citar a publicação
Patinha D,Abreu C,Carvalho C,Cunha OM,Mota M,Afonso J,Sousa T,Albino A,Diniz C,Morato M. Adenosine A<sub>2A</sub> and A<sub>3</sub> Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy. Biomedicines. 2020. 8. (11):p. 1-19. IF:6,081. (1).
