Modulation of the ischemia-induced taurine release by adenosine receptors in the developing and adult mouse hippocampus

Abstract

The release of the inhibitory amino acid taurine is markedly enhanced under ischemic conditions in both adult and developing hippocampus, together with a pronounced increase in the release of excitatory amino acids and the neuromodulator adenosine. We studied the effects of adenosine receptor agonists and antagonists as well as adenosine transport inhibitors on hippocampal [ 3H]taurine release in normoxia and ischemia, using a superfusion system. Under standard conditions the adenosine A 1 receptor agonists N 6-cyclohexyladenosine and R(−) N 6-(2-phenylisopropyl)adenosine potentiated basal taurine release in developing mice and depressed the release in adults in a receptor-mediated manner. Adenosine A 2 receptor compounds had only minor effects on the basal release and the K +-stimulated release was not affected by these drugs. The adenosine uptake inhibitor dipyridamole enhanced basal taurine release in the developing hippocampus and reduced it in the adult. In ischemia the adenosine compounds had no marked effects on taurine release in immature animals, whereas A 1 receptor activation was still able to evoke taurine release in adults by a receptor-mediated mechanism. The results show that the basal release of taurine is modulated by A 1 receptors in both mature and immature hippocampus, whereas in ischemia these receptors potentiate taurine release only in adults. The elevated taurine levels together with the depression of excitatory amino acid release by adenosine receptor activation could be beneficial under ischemic conditions, protecting neural cells against excitotoxicity and hyperexcitation.