MYOCARDIAL ADENYLYL-CYCLASE TYPE-V AND TYPE-VI MESSENGER-RNA - DIFFERENTIAL REGULATION WITH AGE

Myocardial beta-adrenergic signal transduction diminishes with age. Th is decrease is not due to a decrease in the number of beta-adrenocepto rs, but may be a result of an impaired capacity to activate adenylyl c yclase (AC). Forskolin-stimulated AC activity is diminished, and the n umber of forskolin binding sites is decreased, suggesting that the dec rease in signal transduction with age is a result of fewer AC catalyti c units. To investigate whether the decrease in AC with age is associa ted with diminished AC mRNA, we assessed AC type V and type VI mRNA in ventricles from 6-, 11-, and 24-month-old F-344 rats. The predominant mRNA species, type V, increased by 45% between 6 and 11 months of age but decreased to just below the 6-month level by age 24 months. In co ntrast, type VI mRNA decreased by 44% between 6 and 11 months of age a nd then increased to the 6-month level at age 24 months. The changes i n type V and type VI mRNA did not parallel the decreases in the AC act ivity or forskolin binding sites with senescence. These data indicate that the steady-state levels of type V and VI AC mRNA are not reliable predictors of the efficacy of forskolin stimulation of AC activity at different ages.