Age-dependent alteration in cell function of rat salivary glands

研究了大鼠唾液腺药物受体的年龄依赖性改变和核蛋白磷酸化与分泌反应和细胞增殖的关系。与（<^3H>）二氢阿普萘洛尔和（<^3H>）醌酰苯甲酸结合研究显示，大鼠腮腺< α > -、< β > -肾上腺素受体和毒蕈碱受体的数量随年龄变化。然而，这些变化与衰老过程中组织对分泌剂的反应性变化无关。随着年龄的增长，< β > -受体激动剂对< β > -肾上腺素受体的亲和力发生了显著变化，而< β > -受体拮抗剂对< β > -肾上腺素受体的亲和力没有变化。亲和性的年龄依赖性变化与组织对< β > -激动剂的淀粉酶分泌反应相结合。腮腺细胞<Alpha_1> -肾上腺素能刺激钾释放随年龄的增长而下降，这种下降与<Alpha_1> -肾上腺素能反应性的年龄依赖性变化无关。随着年龄的增长，由三磷酸肌醇直接刺激的腮腺细胞的钙外排减少了约50%。差异不是由于老年细胞对磷脂的摄取减少，而是提示与年龄相关的三磷酸肌醇从腮腺细胞内储存的细胞内释放钙的能力缺陷。从异丙肾上腺素处理大鼠的唾液腺核中获得的结果明显表明，非组蛋白的磷酸化在控制DNA复制之前RNA合成的事件中起重要作用。出生后大鼠唾液腺核非组蛋白磷酸化水平明显升高。磷酸化水平在4周龄大鼠达到最大值，并下降到16周龄大鼠。从出生后12个月的大鼠中分离出的核中也保持了这种水平。然而，随着年龄的增长，组蛋白磷酸化没有任何变化。非组蛋白磷酸化的年龄依赖性变化与与染色质相关的蛋白激酶活性的变化相结合。少

Age-dependent alterations of drug receptors and phosphorylation of nuclear proteins in rat salivary glands were studied in relation to the secretory response and the cell proliferation.1. Binding studies with ( <^3H> )dihydroalprenolol and ( <^3H> )quinuclidinyl benzylate showed the age-dependent changes in the number of <alpha> -, <beta> -adrenoceptors and muscarinic receptors in rat parotid glands. However these changes were not coupled with those in responsiveness of the tissues to secretagogues during aging. The affinities of <beta> -agonists, not of <beta> -antagonists, to <beta> -adrenoceptors were significantly changed with increasing age. The age-dependent changes in the affinities were coupled with those in amylase secretory response of the tissues to <beta> -agonists.2. <Alpha_1> -adrenergic stimulated potassium release by parotid cell declined during aging The decline could not be responsible for age-dependent changed in <alpha_1> -adrenergic responsiveness. Calcium efflux s … More timulated directly by inositol triphosphate from parotid cell was reduced by about 50% with increasing age. Differences are not due to a reduction in uptake of the phospholipid into older cells, but suggest and age related defect in the ability of inositol triphosphate to liberate calcium from intracellular store of parotid cells.3. It was obvious from the results obtained by using a salivary gland nuclei isolated from isoproterenol-treated rats that the phosphorylation of the non-histone proteins had an important role in the events controlling the syntheses of RNA which preceeded the replication of DNA. The phosphorylation of non-histone proteins of rat salivary gland nuclei was significantly increased after birth. The levels of phosphorylation reached a maximum at 4-week old rats and declined to those of 16-week old rats. The leveles were also maintained in nuclei isolated from rats of 12 months after birth. However, any changes in the phosphorylation of histone proteins were not observed with increasing age. The age-dependent changes in the phosphorylation of non-histone proteins were coupled with those of protein kinase activities associated with chromatin. Less