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人类逼尿肌β-肾上腺素能受体功能的年龄依赖性变化及其可能机制。

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

作者信息

Li Gang, Li Kai, Li Zhenhua, Wang Ping

机构信息

Department of Urology, the First Affiliated Hospital, Medical University of China, Shenyang 110001, China.

出版信息

Chin Med J (Engl). 2003 Oct;116(10):1511-4.

PMID:14570612
Abstract

OBJECTIVE

To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms.

METHODS

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.

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 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.

摘要

目的

研究β-肾上腺素能反应性随年龄的变化及其可能机制。

方法

采用细胞功能试验,检测了10例老年患者样本对β-肾上腺素能激动剂异丙肾上腺素、BRL37344、福斯高林和二丁酰环磷腺苷(DBcAMP)的反应性。使用非选择性β-肾上腺素能受体配体[3H]-二氢阿普洛尔([3H]-DHA)进行放射性配体结合试验。以10例青年男性的样本作为对照。

结果

对氯化钾的收缩反应无年龄依赖性变化。老年组对异丙肾上腺素、BRL37344和福斯高林的舒张反应分别降低了15.0%、17.6%和12.6%(P<0.001)。异丙肾上腺素和BRL37344的pD2值也显著下降。两组对二丁酰环磷腺苷(DBcAMP)的反应性无差异;最大结合位点随年龄增长显著降低,但平衡解离常数未改变。

结论

β-肾上腺素能反应性存在与年龄相关的下降,这可能是老年人膀胱顺应性降低的致病因素之一。受体密度降低和腺苷酸环化酶活性降低导致的环磷腺苷水平下降可能是β-肾上腺素能反应性变化的潜在分子机制。

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