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The extracellular cyclic AMP-adenosine pathway in renal physiology
Edwin K Jackson1, Dubey K Raghvendra
1Center for Clinical Pharmacology, Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. edj+@pitt.edu
Annual Review of Physiology
|February 24, 2004
Summary
A novel pathway converts extracellular cyclic adenosine monophosphate (cAMP) to adenosine in the kidney, influencing renal function. This process may also involve a pancreatohepatorenal endocrine link.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Adenosine receptors are present in kidney cells, mediating various renal functions.
- Adenosine is endogenously produced in the kidney.
- A novel extracellular cyclic adenosine monophosphate (cAMP)-adenosine pathway for renal adenosine production has been identified.
Purpose of the Study:
- To elucidate the novel extracellular cAMP-adenosine pathway in the kidney.
- To investigate the potential endocrine role of this pathway linking the pancreas, liver, and kidney.
Main Methods:
- The study focuses on biochemical reactions and cellular signaling pathways.
- Analysis of extracellular cAMP conversion to adenosine via ecto-phosphodiesterase and ecto-5'-nucleotidase.
- Examination of the pancreatohepatorenal cAMP-adenosine pathway involving glucagon stimulation of hepatic adenylyl cyclase.
Main Results:
- Extracellular cAMP, produced after adenylyl cyclase activation, is converted to adenosine by ecto-enzymes.
- This local pathway tightly couples adenosine production to receptor sites.
- Hepatic-derived cAMP, filtered and concentrated in renal tubules, can be converted to adenosine, forming a pancreatohepatorenal link.
Conclusions:
- The extracellular cAMP-adenosine pathway provides a localized mechanism for adenosine production in the kidney.
- This pathway may serve as an endocrine communication system between the pancreas, liver, and kidney.