Complex hippocampal responses to ATP: fade due to nucleotidase inhibition and P2-receptor-mediated adenosine release.

When ATP or the related stable analogue, betagamma-imidoATP, were applied to rat hippocampal slices showing population spikes larger than 5 mV peak-to-peak amplitude, a depression of spike size was obtained, which showed a marked fade during the 10-min period of superfusion. The inhibitory responses were prevented by adenosine deaminase or 8-phenyltheophylline. Adenosine responses showed no fade. alphabeta-MethyleneADP enhanced the fade, while suramin at 50 micrometer prevented the early component of the responses. The results suggest that in slices with large population spikes, inhibitory responses to nucleotides are partly due to their conversion to adenosine, and partly due to the activation of P2 receptors which trigger the release of endogenous adenosine.