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′‐triphosphateATP>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. British Journal of Pharmacology (1997) 122, 51–58; doi:10.1038/sj.bjp.0701344