Ozawa H, Ikeda H, Saito T
Department of Neuropsychiatry, Sapporo Medical College, Japan.
Yakubutsu Seishin Kodo. 1989 Dec;9(4):359-68.
Reduced adenylate cyclase (AC) activity of cerebral cortical membrane in the presence of guanine-nucleotide analog [Gpp(NH)p] was observed in 12-month-old rats (aged rats) compared with 2-month-old rats (controls). The EC50 value for Gpp(NH)p activation to AC was slightly but significantly increased in aged rats and the half time for maximal activation of AC by Gpp(NH)p, either with or without isoproterenol was also longer in aged rats. Digitonin-solubilized AC catalytic moiety had a lower activity in the aged rats than in controls. The 125I-pindolol binding to beta-receptor in the cortical membrane from aged rats was decreased. GTP increased the Hill coefficient for isoproterenol displacement binding in controls, but such a change was not noted in aged rats. However, the percent increase of AC activity by 1 microM isoproterenol was greater in aged rats than that in controls. Furthermore, the EC50 value for isoproterenol stimulation of AC in control was lower compared with aged rats. Our results indicate that the decreased AC activity in aged rats may be due to a reduced receptor density, functional changes in GTP-binding protein (G protein) activity, and a reduced catalytic subunit activity. Compensatory changes in the beta receptor-G protein-AC coupling system may also occur during aging.
与2月龄大鼠（对照组）相比，在12月龄大鼠（老年大鼠）中观察到，在鸟嘌呤核苷酸类似物[Gpp(NH)p]存在的情况下，大脑皮质膜的腺苷酸环化酶（AC）活性降低。老年大鼠中Gpp(NH)p激活AC的EC50值略有但显著增加，并且无论有无异丙肾上腺素，Gpp(NH)p使AC达到最大激活的半衰期在老年大鼠中也更长。洋地黄皂苷增溶的AC催化部分在老年大鼠中的活性低于对照组。老年大鼠皮质膜中125I-吲哚洛尔与β受体的结合减少。GTP增加了对照组中异丙肾上腺素置换结合的希尔系数，但在老年大鼠中未观察到这种变化。然而，1μM异丙肾上腺素使AC活性增加的百分比在老年大鼠中高于对照组。此外，对照组中异丙肾上腺素刺激AC的EC50值低于老年大鼠。我们的结果表明，老年大鼠AC活性降低可能是由于受体密度降低、GTP结合蛋白（G蛋白）活性的功能变化以及催化亚基活性降低。在衰老过程中，β受体-G蛋白-AC偶联系统也可能发生代偿性变化。
