Parallel decrease of adenylyl cyclase activity and β1-adrenoceptor density in brain cortex of aging mice

Abstract β -Adrenergic receptors (βARs) and adenylyl cyclase (AC) activity have been found to undergo progressive alterations in the brain cortex of aging mice. In particular, βAR changes are in charge of the β 1 subpopulation ( β 1 AR), β 2 -adrenoceptors ( β 2 ARs) showing no age-related impairments. On these bases, the question arises whether AC alterations can be accounted for by β 1 AR changes or, alternatively, whether there are also receptor independent AC modifications. Experiments have thus been performed on the brain cortex from young and old mice assaying β 1 AR and β 2 AR characteristics and isoproterenol (IPR) and forskolin stimulated AC activity in the same membrane preparations. Other membranes were previously treated with the reducing agent dithiothreitol (DTT) which is known to specifically destroy the binding capacity of β 1 ARs. No statistically significant differences in basal AC activity have been found among the groups studied. Data on IPR-stimulated AC activity in old animals confirm previous findings demonstrating impaired responsiveness when compared with that of young mice. DTT treated membrane preparations from both young and old mice show decreased AC activities. The entity of the decrease is lower in aged animals due to the lower initial level of β 1 ARs. Forskolin stimulation, which is assumed to directly activate AC, has been found impaired in aged mice when compared with young animals, suggesting that also post-receptor alterations occur with advancing age.