Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurones.
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 > or = ATP > adenosine 5'-O-(3-thiotriphosphate)>UTP> alpha, beta-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.
Koizumi
S
S
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Inoue
K
K
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology; D013498:Suramin / Q000494:pharmacology
D018048:Receptors, Purinergic P2; D018698:Glutamic Acid; D013498:Suramin; D000255:Adenosine Triphosphate; D002118:Calcium