Age-related decreases in stimulatory G protein-coupled adenylate cyclase activity in osteoblastic cells

In this study we examined parathyroid hormone (PTH)-, forskolin (FSK)-, and cholera toxin (CTX)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat osteoblastic cells (ROB) isolated from young (4 mo), mature (12 mo), and old (24-28 mo) male rats. Exposure to PTH increased cAMP accumulation in a concentration-dependent manner in all ROB cells examined. However, the maximum response in ROB from young rats was threefold greater than the maximum response in those from mature and old rats. Exposure to FSK also stimulated cAMP accumulation in a concentration-dependent manner, but there were no significant differences in responsiveness among ROB isolated from young, mature, and old rats. Exposure to CTX resulted in a dramatic concentration-dependent increase in cAMP in ROB from young rats but only a modest increase in ROB from mature and old rats. PTH binding kinetics were similar in ROB from rats in each age group. These data suggest an age-related defect in stimulatory G protein coupling to adenylate cyclase, which contributes to decreased osteoblastic responsiveness to PTH.