Distribution and regulation of renal ecto-5'-nucleotidase: implications for physiological functions of adenosine

Adenosine exerts various effects via membrane receptors in the kidney. It reduces the glomerular filtration rate by altering the resistance of the glomerular arterioles, and it inhibits the release of renin as well as neurotransmission. Adenosine receptors have been further found at different levels of the nephron as well as in glomerular cells. Little is known concerning the mechanisms that regulate the extracellular concentration of adenosine, namely, its production, transport, and catabolism. In the present review we first summarize the pathways of adenosine formation. Then we focus on the ecto-5'-nucleotidase, which seems to represent the major source of extracellular adenosine in the kidney; that enzyme is present in tubular luminal membranes, in fibroblasts, and in mesangial cells. In tubules the enzyme probably plays a role in the salvage of nucleotides present in the primary urine. The activity in fibroblasts is strategically located to convert any AMP released by tubules into adenosine in the close vicinity of glomerular arterioles, and it probably plays a predominant role in most of the regulatory mechanisms involving adenosine. Ecto-5'-nucleotidase activity in fibroblasts increases in anemia, maybe as a response to local hypoxia.