Regulation of the ecto-nucleotidase pathway in rat hippocampal nerve terminals

Ecto-nucleotidases play a pivotal role in terminating the signalling via AT P and in producing adenosine, a neuromodulator in the nervous system. We ha ve now investigated the pattern of adenosine formation with different conce ntrations of extracellular ATP in rat hippocampal nerve terminals. It was f ound that adenosine formation is delayed with increasing concentrations of ATP. Also, the rate of adenosine formation increased sharply when the extra cellular concentrations of ATP + ADP decrease below 5 muM, indicating that ATP/ADP feed-forwardly inhibit ecto-5'-nucleotidase allowing a burst-like f ormation of adenosine possibly designed to activate facilitatory A(2A) rece ptors. Initial rate measurements of ecto-5'-nucleotidase in hippocampal ner ve terminals, using IMP as substrate, showed that ATP and ADP are competiti ve inhibitors (apparent K-i of 14 and 4 muM). In contrast, in hippocampal i mmunopurified cholinergic nerve terminals, a burst-like formation of adenos ine is not apparent, suggesting that channelling processes may overcome the feed-forward inhibition of ecto-5'-nucleotidase, thus favouring A(1) recep tor activation.