[Age-dependent alternations in beta-adrenoceptor function in human detrusor and possible mechanism]

Abstract

Objective: To study the age-dependent alternations in beta-adrenergic response and possible mechanism.

Methods: The response to beta-adrenergic agonists isoprenaline and BRL37344, forskolin and dibutyryl cyclic AMP (DBcAMP) of samples from senile people in 10 cases were examined by cellular functional test. Radioligand binding assay was also performed using non-selective beta-adrenergic receptors ligand [(3)H]-dihydroalprenolol ([(3)H]-DHA), the specimens of young men in 10 cases as the control group.

Results: There was no age-dependent change in the contractile response to potassium chloride. The relaxing responses to isoprenaline, BRL37344 and forskolin decreased by 15.0%, 17.6% and 12.6% respectively (P < 0.01). The pD(2) values of the isoprenaline and BRL37344 also declined significantly. There was no difference in the responses to 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 the reduced bladder compliance of the elderly. The decrease of cAMP level caused by the reduced receptor density and adenyl cyclase activity might be the molecular mechanisms underlying the changes of beta-adrenergic responsiveness.