Age-dependent change in the inhibitory effect of an adenosine agonist on hippocampal acetylcholine release in rats

To investigate the possibility that age-dependent deficits in acetylcholine (ACh) release are precipitated by the alteration of endogenous purinergic activities, the effects of (-)N6-phenylisopropyladenosine (PIA), an adenosine agonist, in modulating K+ (25 mM)-induced [3H]ACh release from the hippocampal slices of young (3-6 months old) and old rats (26-30 months old) were examined. In young rats, PIA (0.1-10 microM) caused a dose-related inhibition of [3H]ACh release from the hippocampal slices and a significant reduction in [3H]ACh release was observed in the presence of 1 microM PIA. In old rats, a similar pattern of PIA suppression of K(+)-induced [3H]ACh release was observed; however, a 10-fold higher concentration of PIA (10 microM) was required to elicit a significant inhibition. This age-dependent reduction in responsiveness to PIA may be due to an enhanced endogenous adenosine activity in aged rats leading to downregulation of the adenosine receptors. This notion is supported by the finding that both the adenosine concentration and activity of 5'-nucleotidase, an enzyme partially governing adenosine synthesis, were increased in the hippocampus of old rats as compared to their younger counterparts.