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(American Journal of Pathology. 2005;167:315-325.)
© 2005 American Society for Investigative Pathology

Region-Specific Alterations of Adenosine Receptors Expression Level in Kidney of Diabetic Rat

Tadeusz Pawelczyk*, Marzena Grden*, Robert Rzepko{dagger}, Monika Sakowicz* and Andrzej Szutowicz{ddagger}

From the Departments of Molecular Medicine,* Pathomorphology,{dagger} and Laboratory Medicine,{ddagger} Medical University of Gdansk, Gdansk, Poland

Pathological alterations of renal function in insulin-dependent diabetes have been attributed to numerous factors, including adenosine. This study examined the expression levels of adenosine receptors (ARs) in the kidney of the streptozotocin-induced diabetic rat. In the diabetic kidney A1-AR mRNA levels increased 1.7- and 2.8-fold in cortex and medulla, respectively. This was accompanied by increased A1-AR protein levels in membranes of kidney cortex (1.5-fold) and medulla (threefold). A1-AR immunoreactivity increased strongly along medullar tubules especially in the collecting duct. The levels of A2a-AR mRNA increased twofold in diabetic kidney cortex but remained unchanged in medulla; however, A2a-AR protein levels increased more than threefold in cortex. Immunohistochemistry showed increased A2a-AR immunoreactivity in luminal membranes of cortical collecting ducts and in epithelial cells of preglomerular vessels. There were no significant changes in A2b-AR expression in diabetic kidney except in medullar membranes, where the receptor protein content decreased by 60%. A3-AR mRNA levels in diabetic kidney remained unchanged, but membrane-associated A3-AR protein levels increased by 70% in diabetic kidney cortex and decreased by 80% in medulla. These changes in ARs genes expression, receptor protein content, and cellular and tissue distribution, correspond to abnormalities characteristic of the diabetic kidney, suggesting involvement in pathogenesis of diabetic nephropathy.




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