Region-specific alterations of adenosine receptors expression level in kidney of diabetic rat.
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.
Pawelczyk
Tadeusz
T
Department of Molecular Medicine, Medical University of Gdansk, ul. Debinki 7, paw. 29, 80-211 Gdansk, Poland. tkpaw@amg.gda.pl
Grden
Marzena
M
Rzepko
Robert
R
Sakowicz
Monika
M
Szutowicz
Andrzej
A
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin; D014018:Tissue Distribution
D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D013311:Streptozocin