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Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms
1Department of Urology, the First Affiliated Hospital, Medical University of China, Shenyang 110001, China.
Chinese Medical Journal
|October 23, 2003
Summary
Aging reduces beta-adrenergic responsiveness, potentially impacting bladder function. This decline may stem from lower receptor density and adenylyl cyclase activity, affecting cyclic AMP levels.
Area of Science:
- Pharmacology
- Gerontology
- Physiology
Background:
- Beta-adrenergic signaling plays a crucial role in various physiological processes, including smooth muscle function.
- Age-related changes in cellular signaling pathways can lead to functional deficits in older individuals.
Purpose of the Study:
- To investigate age-dependent alterations in beta-adrenergic receptor responsiveness.
- To explore the underlying molecular mechanisms contributing to these changes.
Main Methods:
- Cellular function tests assessed responsiveness to beta-adrenergic agonists (isoprenaline, BRL37344, forskolin) and dibutyryl cyclic AMP (DBcAMP).
- Radioligand binding assays using [3H]-dihydroalprenolol ([3H]-DHA) quantified beta-adrenergic receptor density and affinity.
- Samples from older patients were compared with those from young men.
Main Results:
- Aged individuals exhibited significantly reduced relaxation responses to isoprenaline, BRL37344, and forskolin.
- The potency (pD2 values) for isoprenaline and BRL37344 was diminished in the elderly.
- While responsiveness to DBcAMP remained unchanged, a significant decrease in maximum binding sites for beta-adrenergic receptors was observed with age.
Conclusions:
- Age-related decline in beta-adrenergic responsiveness is evident, potentially contributing to reduced bladder compliance in the elderly.
- Reduced cyclic AMP (cAMP) levels, stemming from decreased receptor density and adenylyl cyclase activity, likely underlie the observed changes in beta-adrenergic responsiveness.
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