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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.
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 The contractile response 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 . 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.