Myocardial adenylyl cyclase type V and VI mRNA: differential regulation with age.
Myocardial beta-adrenergic signal transduction diminishes with age. This decrease is not due to a decrease in the number of beta-adrenoceptors, but may be a result of an impaired capacity to activate adenylyl cyclase (AC). Forskolin-stimulated AC activity is diminished, and the number of forskolin binding sites is decreased, suggesting that the decrease in signal transduction with age is a result of fewer AC catalytic units. To investigate whether the decrease in AC with age is associated 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 contrast, type VI mRNA decreased by 44% between 6 and 11 months of age and then increased to the 6-month level at age 24 months. The changes in type V and type VI mRNA did not parallel the decreases in the AC activity 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.
Scarpace
P J
PJ
Department of Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Center, Gainesville, Florida 32608-1197, USA.
Matheny
M
M
Tümer
N
N
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001665:Binding Sites; D005576:Colforsin / Q000378:metabolism / Q000494:pharmacology*; D006352:Heart Ventricles / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction
D007527:Isoenzymes; D012333:RNA, Messenger; D005576:Colforsin; D000262:Adenylyl Cyclases