Mechanism of the inhibitory action of ATP in rat hippocampus

We have already shown, by calcium imaging with an electrophysiological method and direct detection of glutamate, that ATP inhibits the glutamate release from cultured rat hippocampus [Koizumi and Inoue, 1997; Inoue et al., 1999], although ATP induces fast synaptic currents and produces an increase in intracellular calcium in a subpopulation of cultured hippocampal neurons [Inoue et al., 1992; Inoue et al., 1995]. We have examined the mechanism of the inhibition by ATP using the FM1-43 method as well as the methods mentioned above. Our results suggest that ATP stimulates G protein-coupled P2Y receptors locating in the presynaptic nerve ending to activate PLCβ, presumably resulting in the inhibition of presynaptic N-and P/Q-type voltage-gated calcium channels. Meanwhile, ATP stimulates the release of GABA, an inhibitory neurotransmitter that inhibits the excitable function of glutamate. Besides these actions of ATP on the regulation of neurotransmitters, it is already reported that ATP also activates microglia cells to release plasminogen [Inoue et al., 1998] and IL-6 [Shigemoto et al., 2000], which were reported to act as neurotrophic factors. Taken together, these data suggest that ATP may protect the hippocampal function from excess stimulation.