Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms.
OBJECTIVE
To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms.


METHODS
Responsiveness to the beta-adrenergic agonists isoprenaline, BRL37344, forskolin, and dibutyryl cyclic AMP (DBcAMP) was examined in samples from 10 older patients by using a cellular function test. A radioligand binding assay was performed using the non-selective beta-adrenergic receptor ligand [3H]-dihydroalprenolol ([3H]-DHA). Specimens from 10 young men were used as controls.


RESULTS
There were no age-dependent changes in contractile response to KCl. The relaxation responses to isoprenaline, BRL37344, and forskolin decreased in the aged group by 15.0%, 17.6%, and 12.6%, respectively (P < 0.001). The pD2 values for isoprenaline and BRL37344 also declined significantly. There was no difference in the responsiveness to dibutyryl cyclic AMP (DBcAMP) between the two groups; the maximum binding site decreased significantly with increasing age, but the equilibrium-dissociation constant did not change.


CONCLUSIONS
There is an age-related decline in beta-adrenergic responsiveness which might be one of the causative factors of reduced bladder compliance in the elderly. A decrease in cAMP level caused by reduced receptor density and adenylyl cyclase activity might be the underlying molecular mechanism of the changes in beta-adrenergic responsiveness.
Li
Gang
G
Department of Urology, the First Affiliated Hospital, Medical University of China, Shenyang 110001, China.
Li
Kai
K
Li
Zhenhua
Z
Wang
Ping
P
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta