Role of the extracellular cAMP-adenosine pathway in renal physiology

Adenosine exerts physiologically significant receptor-mediated effects on r enal function. For example, adenosine participates in the regulation of pre glomerular and postglomerular vascular resistances, glomerular filtration r ate, renin release, epithelial transport, intrarenal inflammation, and grow th of mesangial and vascular smooth muscle cells. It is important, therefor e, to understand the mechanisms that generate extracellular adenosine withi n the kidney. In addition to three "classic" pathways of adenosine biosynth esis, contemporary studies are revealing a novel mechanism for renal adenos ine production termed the "extracellular cAMP-adenosine pathway." The extra cellular cAMP-adenosine pathway is defined as the egress of cAMP from cells during activation of adenylyl cyclase, followed by the extracellular conve rsion of cAMP to adenosine by the serial actions of ecto-phosphodiesterase and ecto-5'-nucleotidase. This mechanism of extracellular adenosine product ion may provide hormonal control of adenosine levels in the cell-surface bi ophase in which adenosine receptors reside. Tight coupling of the site of a denosine production to the site of adenosine receptors would permit a low-c apacity mechanism of adenosine biosynthesis to have a large impact on adeno sine receptor activation. The purposes of this review are to summarize the physiological roles of adenosine in the kidney; to describe the classic pat hways of renal adenosine biosynthesis; to review the evidence for the exist ence of the extracellular cAMP-adenosine pathway; and to describe possible physiological roles of the extracellular cAMP-adenosine pathway, with parti cular emphasis on the kidney.