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

• Published in: Chinese medical journal Vol. 116; no. 10; pp. 1511 - 1514
• Main Author: 李刚 李凯 李振华 王平
• Format: Journal Article
• Language: English
• Published: China Department of Urology, the First Affiliated Hospital, Medical University of China, Shenyang 110001, China 01.10.2003
• Subjects: Adrenergic beta-Agonists - pharmacology; Age Factors; Aged; Aging - physiology; Female; Humans; Male; Middle Aged; Muscle Contraction - physiology; Muscle, Smooth - physiology; Radioligand Assay; Receptors, Adrenergic, beta - physiology; Urinary Bladder - physiology; β-肾腺素受体; 分子机制; 逼尿肌; 遗传学; β-adrenergic receptors; bladder smooth muscle; detrusors
• ISSN: 0366-6999; 2542-5641

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 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.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.