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Age-associated decrease in vasopressin-induced renal water transport: a role for adenylate cyclase and G protein
1Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson (formerly Rutgers) Medical School, Piscataway, N.J. 08854-5635.
Gerontology
|January 1, 1992
Summary
Aging impairs kidney function by reducing the response to arginine vasopressin (AVP). This study found age-related declines in kidney tubules were due to issues with Gs proteins and adenylate cyclase, not receptor changes.
Area of Science:
- Nephrology
- Gerontology
- Molecular Biology
Background:
- Aging is linked to reduced renal concentrating ability.
- Dehydration triggers arginine vasopressin (AVP) release, impacting kidney function.
Purpose of the Study:
- To investigate age-related changes in the sensitivity of kidney tubules to AVP.
- To identify the molecular mechanisms behind decreased renal concentrating ability in aging rabbits.
Main Methods:
- Microdissection of cortical collecting tubules (CCT) from rabbits of different ages (young, middle-aged, old).
- In vitro perfusion analysis and tissue culture of CCT epithelial monolayers.
- Measurement of osmotic fluid transport, adenylate cyclase activity, and [3H]-AVP binding.
Main Results:
- An age-associated decline in osmotic fluid transport and adenylate cyclase activity in response to AVP was observed.
- [3H]-AVP binding and hydraulic conductivity were not significantly different between young and old CCT.
- Cholera toxin and forskolin showed reduced efficacy in old CCT, indicating impaired downstream signaling.
Conclusions:
- The age-related decline in CCT response to AVP is not due to receptor alterations or post-cAMP events.
- Alterations in Gs proteins and the catalytic unit of adenylate cyclase are responsible for the diminished AVP response in aging kidneys.