Age-dependent changes in β-adrenoceptor function in human detrusors and possible mechanisms

摘要

Objective To study age-dependent changes in β-adrenergic responsiveness and their possible mechanisms. Methods Responsiveness to the β-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 β-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 pD_2 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 β-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 β-adrenergic responsiveness.