Derweesh I H, Wheeler M A, Weiss R M
Section of Urology, Yale University School of Medicine, New Haven, CT 06520-8041, USA.
J Pharmacol Exp Ther. 2000 Sep;294(3):969-74.
Decreased response of bladder to beta-adrenergic stimulation with aging is related to decreased adenylyl cyclase activity and possibly to changes in guanine nucleotide regulatory protein (G-protein) content or function. G-protein content was quantified by Western blot analysis using antibodies to Gsalpha, Goalpha, and Gialpha in 21-day-old (weanling), 90-day-old (young adult), 6-month-old (adult), and 24-month-old (old) rat bladders. Gi/Go function in bladders with aging was measured by ADP-ribosylation with pertussis toxin. Content of Gsalpha, Goalpha, and Gialpha was lower in 90-day-old bladder than in 21-day-old bladder. Gsalpha content was similar in the 21-day-, 6-month-, and 24-month-old bladders. Gialpha content as well as pertussis toxin-catalyzed ADP-ribosylation was higher in 24-month-old bladders than in 21- and 90-day-old bladders. Pertussis toxin-catalyzed ADP-ribosylation of bladder membranes and treatment of bladder with protein kinase A inhibitors reversed the age-dependent decline in isoproterenol stimulation of adenylyl cyclase. Decreases in beta-adrenergic-induced relaxation response with age in rat bladder are due in part to increases in the content and functional activity of pertussis toxin-sensitive G-protein.
随着衰老，膀胱对β-肾上腺素能刺激的反应性降低与腺苷酸环化酶活性降低有关，可能还与鸟嘌呤核苷酸调节蛋白（G蛋白）含量或功能的变化有关。使用针对Gsα、Goα和Giα的抗体，通过蛋白质印迹分析对21日龄（断奶）、90日龄（年轻成年）、6月龄（成年）和24月龄（老年）大鼠膀胱中的G蛋白含量进行定量。用百日咳毒素进行ADP-核糖基化来测量衰老膀胱中的Gi/Go功能。90日龄膀胱中Gsα、Goα和Giα的含量低于21日龄膀胱。21日龄、6月龄和24月龄膀胱中Gsα的含量相似。24月龄膀胱中Giα的含量以及百日咳毒素催化的ADP-核糖基化高于21日龄和90日龄膀胱。百日咳毒素催化的膀胱膜ADP-核糖基化以及用蛋白激酶A抑制剂处理膀胱可逆转异丙肾上腺素刺激腺苷酸环化酶时的年龄依赖性下降。大鼠膀胱中β-肾上腺素能诱导的舒张反应随年龄下降部分是由于百日咳毒素敏感G蛋白的含量和功能活性增加。
