Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurones

Abstract

1. The effect of adenosine 5'-triphosphate (ATP) on glutamatergic synaptic transmission in hippocampus was examined by an indicator of intracellular Ca2+ oscillations. These oscillations were postsynaptic responses by glutamate released from presynaptic sites. ATP completely inhibited the oscillations in a concentration-dependent manner. 2. The ATP-induced inhibition was mediated via P2-purinoceptors since ATP exhibited the inhibitory action even in the presence of P1-purinoceptor antagonists. Also non-hydrolysable ATP analogues and uridine 5'-triphosphate (UTP) inhibited the oscillation. 3. The rank order of agonist potency of ATP analogues for inhibition of the Ca2+ oscillation was as follows: 2-methyl-thio-adenosine 5'-triphosphate ≤ ATP > adenosine 5'-O-(3-thiotriphosphate) > UTP > α,β-methylene-adenosine 5'-triphosphate. These inhibitory effects were insensitive to suramin. Judging from this rank order of potency, the inhibitory P2-purinoceptor could be assigned to a subclass of GTP-binding protein coupled-type receptors. 4. The site of action of ATP was thought to be presynaptic since ATP did not affect the postsynaptic Ca2+ responses by glutamate. These results suggest the existence of a presynaptic inhibitory P2-receptor that inhibits glutamate release in the hippocampus.