Gettys T W, Rohlfs E M, Prpic V, Daniel K W, Taylor I L, Collins S
Department of Medicine, Medical University of South Carolina, Charleston 29425, USA.
Endocrinology. 1995 May;136(5):2022-32. doi: 10.1210/endo.136.5.7720650.
Epididymal adipocytes were isolated from Fischer 344 rats aged 3, 6, 12, and 24 months, to study the mechanisms responsible for age-dependent diminution in cellular adrenergic responsiveness. Messenger RNA (mRNA) levels for the beta 1-, beta 2-, and beta 3-adrenergic receptors (ARs) were compared across age groups and related to adenylyl cyclase activation by selective receptor agonists in adipocyte plasma membranes and activation of lipolysis in intact cells. mRNA levels for the beta 1-AR decreased by 60% between 3-6 months and remained at this reduced level through 12 and 24 months. A modest increase in beta 2-AR mRNA was noted between 3-12 months, but decreased between 12-24 months to levels seen in the 3-month-old group. mRNA for the beta 3-AR did not change between 3-6 months, but decreased by about 40% between 6-12 months, and by a further 50% between 12-24 months. Lipolytic responsiveness also diminished with age, and regardless of whether beta 3-selective or beta 1/beta 2-selective agonists were used, the maximal release of glycerol was most severely blunted in adipocytes from 24-month-old rats. The age-dependent changes in adenylyl cyclase activation by beta-adrenergic agonists mirrored the observed changes in lipolytic responsiveness with respect to diminished efficacy. These results together with the similar forskolin-stimulated adenylyl cyclase activity among the groups suggest age-dependent changes in activation of adenylyl cyclase at a prior step. This suggestion is also supported by the comparable inhibitory capacities of the alpha 2-adrenergic and A1-adenosine signaling systems among the age groups. In view of the similar levels of Gs alpha, the age-dependent decrease in adrenergic responsiveness in rat adipocytes appears to result primarily from specific decreases in the expression of both beta 3-AR and beta 1-ARs.
从3、6、12和24月龄的Fischer 344大鼠中分离附睾脂肪细胞，以研究导致细胞肾上腺素能反应性随年龄下降的机制。比较各年龄组β1-、β2-和β3-肾上腺素能受体（ARs）的信使核糖核酸（mRNA）水平，并将其与脂肪细胞质膜中选择性受体激动剂激活腺苷酸环化酶以及完整细胞中脂解激活情况相关联。β1-AR的mRNA水平在3至6个月之间下降了60%，并在12个月和24个月时维持在这一降低水平。β2-AR mRNA在3至12个月之间有适度增加，但在12至24个月之间下降至3月龄组的水平。β3-AR的mRNA在3至6个月之间没有变化，但在6至12个月之间下降了约40%，在12至24个月之间又进一步下降了50%。脂解反应性也随年龄下降，无论使用β3-选择性还是β1/β2-选择性激动剂，24月龄大鼠脂肪细胞中甘油的最大释放量受到的抑制最为严重。β-肾上腺素能激动剂激活腺苷酸环化酶的年龄依赖性变化反映了脂解反应性在效能降低方面的观察变化。这些结果以及各组间佛司可林刺激的腺苷酸环化酶活性相似表明，腺苷酸环化酶激活在先前步骤存在年龄依赖性变化。各年龄组α2-肾上腺素能和A1-腺苷信号系统的可比抑制能力也支持了这一观点。鉴于Gsα水平相似，大鼠脂肪细胞中肾上腺素能反应性的年龄依赖性下降似乎主要是由于β3-AR和β1-ARs表达的特异性降低所致。
