Extracellular cAMP-adenosine pathways in the mouse kidney.

Area of Science:

• Biochemistry
• Renal Physiology
• Molecular Biology

Background:

• Extracellular cyclic adenosine monophosphate (cAMP) pathways contribute to renal adenosine production.
• Mouse kidneys are valuable models for studying renal adenosine production, especially in genetically modified contexts.

Purpose of the Study:

• To investigate the presence and function of renal extracellular 2',3'-cAMP-adenosine and 3',5'-cAMP-adenosine pathways in mouse kidneys.
• To determine the impact of energy depletion on these pathways.
• To elucidate the role of CD73 in the 3',5'-cAMP-adenosine pathway.

Main Methods:

• Isolated, perfused mouse kidneys were infused with 2',3'-cAMP and 3',5'-cAMP.
• Renal venous secretion rates of cAMPs, AMPs, adenosine, and inosine were measured.
• Experiments were conducted under basal conditions and following energy depletion using metabolic inhibitors.
• Comparisons were made between wild-type and CD73 knockout mouse kidneys.

Main Results:

• Both 2',3'-cAMP and 3',5'-cAMP infusions led to increased secretion of their corresponding AMPs and adenosine.
• Energy depletion significantly increased the secretion of 2',3'-cAMP, AMPs, adenosine, and inosine, but not 3',5'-cAMP.
• CD73 deficiency attenuated the 3',5'-cAMP-induced increase in 5'-AMP and inosine, but adenosine levels remained similar.

Conclusions:

• Mouse kidneys metabolize extracellular 2',3'-cAMP and 3',5'-cAMP to adenosine via AMP intermediates.
• The 2',3'-cAMP-adenosine pathway is activated by energy depletion, while the 3',5'-cAMP-adenosine pathway is not.
• While CD73 plays a role in the 3',5'-cAMP pathway, alternative metabolic routes and reduced adenosine breakdown compensate for its absence.