Yono Makoto, Foster Harris E, Weiss Robert M, Latifpour Jamshid
Section of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Urol. 2006 Sep;176(3):1214-9. doi: 10.1016/j.juro.2006.04.038.
Because age related changes occur in the properties of alpha(1)-adrenoceptor in several mammalian tissues and alpha(1)-adrenoceptor antagonists are extensively used to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, we investigated age related changes in the functional, biochemical and molecular properties of alpha(1)-adrenoceptor in the rat genitourinary tract.
The characteristics of alpha(1)-adrenoceptor in the ventral and dorsolateral prostate, and bladder base and dome of 3 and 22-month-old rats were determined using an isolated muscle bath, radioligand receptor binding and real-time reverse transcriptase-polymerase chain reaction techniques.
Old rats had significantly higher body weight, lower testosterone, a smaller ventral prostate and a larger bladder dome than young rats. Although there was no significant age dependent difference in the properties of alpha(1)-adrenoceptor in the bladder base and dome, total alpha(1)-adrenoceptor density, mRNA expression of all 3 alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) and the maximum contractile responses to phenylephrine were significantly lower in the ventral and dorsolateral prostate of 22 vs 3-month-old rats.
Age related differences in the molecular, biochemical and functional properties of alpha(1)-adrenoceptors in the rat genitourinary tract may indicate potential differences in the response to alpha(1)-adrenoceptor antagonists with aging, ie a decrease in the therapeutic response in old vs young rats in the response to alpha(1)-adrenoceptor antagonists when used to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia.
由于多种哺乳动物组织中α(1)-肾上腺素能受体的特性会随年龄发生变化,且α(1)-肾上腺素能受体拮抗剂被广泛用于治疗良性前列腺增生继发的下尿路症状,我们研究了大鼠泌尿生殖道中α(1)-肾上腺素能受体在功能、生化和分子特性方面的年龄相关变化。
采用离体肌槽、放射性配体受体结合及实时逆转录-聚合酶链反应技术,测定3月龄和22月龄大鼠腹侧和背外侧前列腺以及膀胱底部和顶部的α(1)-肾上腺素能受体特征。
老年大鼠体重显著高于年轻大鼠,睾酮水平较低,腹侧前列腺较小,膀胱顶部较大。虽然膀胱底部和顶部的α(1)-肾上腺素能受体特性在年龄上无显著差异,但22月龄大鼠腹侧和背外侧前列腺的总α(1)-肾上腺素能受体密度、所有3种α(1)-肾上腺素能受体亚型(α(1A)、α(1B)和α(1D))的mRNA表达以及对去氧肾上腺素的最大收缩反应均显著低于3月龄大鼠。
大鼠泌尿生殖道中α(