Atypical pattern of adenylyl cyclase activity in the adrenal medulla with age

Concurrent reduced physiological responsiveness often occurs in those tissues in which signal transduction coupled to adenylyl cyclase is diminished with age. In the adrenal medulla, the major physiological functions are catecholamine synthesis and release, and these functions are increased with age. To examine whether the sensitivity or efficacy for adenylyl cyclase stimulation is altered with age, we determined the vasoactive intestinal peptide (VIP) and forskolin activation of adenylyl cyclase in adrenal medullary membranes from young (4 month) and senescent (24 month) male F-344 rats. Stimulation by VIP (10 microns) and GTP (10 microns) were unchanged with age. In contrast, the maximal stimulation by forskolin (100 microns) and the sensitivity for forskolin stimulation were increased with age. These data indicate that the pattern of increased adenylyl cyclase stimulation with age is comparable to that in liver tissue but atypical with respect to all other tissues in the rat.