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Parallel modification of adenosine extracellular metabolism and modulatory action in the hippocampus of aged rats
Author(s) -
Cunha Rodrigo A.,
Almeida Teresa,
Ribeiro J. A.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00095.x
Subject(s) - adenosine , extracellular , adenosine a1 receptor , adenosine receptor , purinergic signalling , medicine , endocrinology , neuromodulation , 5' nucleotidase , adenosine a3 receptor , adenosine a2a receptor , chemistry , agonist , receptor , biology , biochemistry , stimulation
The neuromodulator adenosine can be released as such, mainly activating inhibitory A 1 receptors, or formed from released ATP, preferentially activating facilitatory A 2A receptors. We tested if changes in extracellular adenosine metabolism paralleled changes in A 1 /A 2A receptor neuromodulation in the aged rat hippocampus. The evoked release and extracellular catabolism of ATP were 49–55% lower in aged rats, but ecto‐5′‐nucleotidase activity, which forms adenosine, was 5‐fold higher whereas adenosine uptake was decreased by 50% in aged rats. The evoked extracellular adenosine accumulation was 30% greater in aged rats and there was a greater contribution of the ecto‐nucleotidase pathway and a lower contribution of adenosine transporters for extracellular adenosine formation in nerve terminals. Interestingly, a supramaximal concentration of an A 1 receptor agonist, N 6 ‐cyclopentyladenosine (250 n m ) was less efficient in inhibiting (17% in old versus 34% in young) and A 2A receptor activation with 30 n m CGS21680 was more efficient in facilitating (63% in old versus no effect in young) acetylcholine release from hippocampal slices of aged compared with young rats. The parallel changes in the metabolic sources of extracellular adenosine and A 1 /A 2A receptor neuromodulation in aged rats further strengthens the idea that different metabolic sources of extracellular adenosine are designed to preferentially activate different adenosine receptor subtypes.