Article date: December 2000
By: A M Sebastião, R A Cunha, A De Mendonça, J A Ribeiro in Volume 131, Issue 8, pages 1629-1634
We compared the modulation of synaptic transmission by adenosine A1 receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks).
The adenosine A1 receptor agonist, N6‐cyclopentyladenosine, was less potent (P<0.05) to inhibit synaptic transmission in aged (EC50=53 nM) than young adult (EC50=14 nM) hippocampal slices, these effects being prevented by the A1 receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX).
In contrast with the lower effect of the A1 receptor agonist, it was observed that blockade of A1 receptors with DPCPX (50 nM), or removal of endogenous extracellular adenosine with adenosine deaminase (2 u ml−1), caused a more pronounced disinhibition of synaptic transmission in aged rats. Also consistent with a more intense A1 receptor‐mediated inhibitory tonus by endogenous adenosine in aged rats was the finding that to fully prevent the depression of synaptic transmission induced by 3 min hypoxia, a higher concentration of DPCPX was required in slices from aged (100 nM) than from young (50 nM) rats.
It is concluded that in hippocampal slices of aged rats the efficiency of A1 receptors to modulate synaptic transmission is reduced, but this may be compensated by an enhanced inhibitory tonus by endogenous adenosine.
We compared the modulation of synaptic transmission by adenosine A1 receptors in the hippocampus of aged (24 months) and young adult rats (6 weeks).
The adenosine A1 receptor agonist, N6‐cyclopentyladenosine, was less potent (P<0.05) to inhibit synaptic transmission in aged (EC50=53 nM) than young adult (EC50=14 nM) hippocampal slices, these effects being prevented by the A1 receptor antagonist, 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX).
In contrast with the lower effect of the A1 receptor agonist, it was observed that blockade of A1 receptors with DPCPX (50 nM), or removal of endogenous extracellular adenosine with adenosine deaminase (2 u ml−1), caused a more pronounced disinhibition of synaptic transmission in aged rats. Also consistent with a more intense A1 receptor‐mediated inhibitory tonus by endogenous adenosine in aged rats was the finding that to fully prevent the depression of synaptic transmission induced by 3 min hypoxia, a higher concentration of DPCPX was required in slices from aged (100 nM) than from young (50 nM) rats.
It is concluded that in hippocampal slices of aged rats the efficiency of A1 receptors to modulate synaptic transmission is reduced, but this may be compensated by an enhanced inhibitory tonus by endogenous adenosine.
British Journal of Pharmacology (2000) 131, 1629–1634; doi:10.1038/sj.bjp.0703736
DOI: 10.1038/sj.bjp.0703736
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