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

摘要

abstract_textpObjective To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms./ppMethods 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 p-adrenergic receptor ligand H-3-dihydroalprenolol (H-3-DHA). Specimens from 10 young men were used as controls./ppResults 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./ppConclusions 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 P-adrenergic responsiveness./p/abstract_text