INFLUENCE OF MG2-VITRO RESPONSIVENESS OF ADENYLATE-CYCLASE FROM HEARTS OF AGING RATS( ON THE IN)

The influence of [Mg2+] on the basal or stimulated activity of adenyla te cyclase from the hearts of young (1 month old) and aged (24 months old) rats has been investigated in vitro. The basal activity of cardia c adenylate cyclase, and its responsiveness to stimulatory or inhibito ry effectors, declined with age. This is probably due to alterations a t the catalytic moiety of the signal transduction system, such as an i mpairment in the affinity of the catalytic moiety for ATP and a lower capacity of the catalytic moiety to bind activated stimulatory (Gs) or inhibitory (Gi) guanine nucleotide binding proteins. Compared to the enzyme from the heart of aged rats, unstimulated adenylate cyclase fro m the heart of young rats was more sensitive to an increase in [Mg2+] in the incubation mixture as shown by a greater increase in basal acti vity and in the affinity of the enzyme for ATP. An increase in [Mg2+] counteracted the inhibitory effect of spermine on adenylate cyclase mo re effectively in young rats than in aged rats, On the other band, an increase in [Mg2+] facilitated the stimulation of adenylate cyclase by Gpp(NH)p, isoproterenol and forskolin more in aged rats than in young rats. GDPbetaS prevented the positive effect of high [Mg2+] on the st imulation of adenylate cyclase by forskolin, suggesting that an increa sed [Mg2+]favors the activation of Gs or the formation of functional c omplexes between the catalytic moiety and Gs. We suggest that aging le ads to a higher requirement for Mg2+ at the allosteric site on the cat alytic moiety whose occupancy is essential for the full expression of stimulated activity.