Mechanism of the inhibitory action of ATP in rat hippocampus

Abstract

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., 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 ] 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. Drug Dev. Res. 52:95-103, 2001.

P2Y receptor regulation of cultured rat cerebral cortical cells: calcium responses and mRNA expression in neurons and glia

“…There is a body of evidence that provides a clear indication of a widespread role for P2Y receptors in rat cerebral neurons–a presynaptic role on nerve terminals. Accordingly, several reports have shown that release of biogenic amines (noradrenaline, dopamine and 5‐hydroxytryptamine) and glutamate is regulated by presynaptic P2Y receptors (von Kugelgen et al ., 1994; Koch et al ., 1995; 1997; Zhang et al ., 1995; Bennett & Boarder, 2000; Inoue & Koizumi, 2001). From the current studies there emerges evidence for a second role for P2Y receptors in rat brain: glial cells are apparently influenced by nucleotides via a phospholipase C‐coupled P2Y 1 receptors.…”

“…Initially this related to presynaptic P2Y receptor regulation of release of the amines noradrenaline, 5‐hydroxytryptamine and dopamine (von Kugelgen et al ., 1994; Koch et al ., 1995; 1997; Krugel et al ., 2001a, 2001b). However, we and others have recently presented evidence that directly implicates P2Y receptors in the presynaptic regulation of glutamate release (Bennett & Boarder, 2000; Inoue & Koizumi, 2001). These investigations suggest a widespread influence of P2Y receptors on brain function.…”