Wheeler M A, Housman A, Cho Y H, Weiss R M
J Pharmacol Exp Ther. 1986 Oct;239(1):99-103.
Adenylate cyclase activity was measured in ureteral homogenates from guinea pigs of five age groups, ranging from neonates to older adults (retired breeders). Isoproterenol stimulation of adenylate cyclase activity is lost completely in ureters from 90 day and older animals. Forskolin activation also declines rapidly with increasing age; there is a significant (39%) decrease in activation at 30 days when compared to 10-day values with a further decline at 90 days. At 90 days, NaF, GTP and 5'-guanylimido-diphosphate stimulation of adenylate cyclase decreases by only 1, 9 and 23%, respectively, from the 10-day values. Prostaglandin E1 stimulation over 5'-guanylimido-diphosphate control does not decrease with age. 5'-Guanylimido-diphosphate in the presence of ethanol, activates adenylate cyclase to a greater extent in the older animals. These data may suggest that the decreased ability to activate adenylate cyclase with age may be due to a loss of the efficiency of coupling in the more rigid aged membranes. Other explanations include loss of catalytic function with age. The loss of adenylate cyclase activity in aging correlates well with our previously reported study showing that isoproterenol causes a greater decrease in contractility of ureters from younger than from older guinea pigs.
在五个年龄组的豚鼠输尿管匀浆中测量了腺苷酸环化酶活性，这些年龄组从新生豚鼠到老年豚鼠（退休繁殖种豚）。在90日龄及以上动物的输尿管中，异丙肾上腺素对腺苷酸环化酶活性的刺激作用完全丧失。随着年龄增长，福斯高林激活作用也迅速下降；与10日龄时相比，30日龄时激活作用显著下降（39%），90日龄时进一步下降。在90日龄时，与10日龄时的值相比，NaF、GTP和5'-鸟苷亚胺二磷酸对腺苷酸环化酶的刺激作用分别仅下降1%、9%和23%。前列腺素E1相对于5'-鸟苷亚胺二磷酸对照的刺激作用不会随年龄而降低。在老年动物中，乙醇存在下的5'-鸟苷亚胺二磷酸能更大程度地激活腺苷酸环化酶。这些数据可能表明，随着年龄增长激活腺苷酸环化酶的能力下降可能是由于在更僵硬的老年细胞膜中偶联效率的丧失。其他解释包括随着年龄增长催化功能的丧失。衰老过程中腺苷酸环化酶活性的丧失与我们之前报道的研究结果很好地相关，该研究表明异丙肾上腺素导致年轻豚鼠输尿管收缩性的下降比老年豚鼠更大。
