Age dependence of adenylate cyclase in guinea pig ureter homogenate.

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.