Concurrent reduced physiological responsiveness often occurs in those
tissues in which signal transduction coupled to adenylyl cyclase is di
minished with age. In the adrenal medulla, the major physiological fun
ctions are catecholamine synthesis and release, and these functions ar
e increased with age. To examine whether the sensitivity or efficacy f
or adenylyl cyclase stimulation is altered with age, we determined the
vasoactive intestinal peptide (VIP) and forskolin activation of adeny
lyl cyclase in adrenal medullary membranes from young (4 month) and se
nescent (24 month) male F-344 rats. Stimulation by VIP (10 mu m) and G
TP (10 mu m) were unchanged with age. in contrast, the maximal stimula
tion by forskolin (100 mu m) and the sensitivity for forskolin stimula
tion 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.