Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms / 中华医学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>