Absence of P2-purinoceptors in hippocampal pathways

1. Many apparent actions of adenosine 5'-triphosphate (ATP) are mediated by adenosine produced by enzymatic hydrolysis of the nucleotide. Previously described actions of ATP in the CNS have been partly due to this phenomenon. In the present study analogues of ATP, which are not hydrolysed to adenosine, were used to seek responses to activating nucleotide (P2) receptors in the hippocampus. The analogues used were L-adenosine-5'-(beta,gamma-methylene)-triphosphonate and 2-methylthioadenosine-5'-(beta,gamma-difluoromethylene)-triphosphonat e. 2. Neither of the stable nucleotides had any effect on orthodromically evoked synaptic potentials in the CA1 region of rat hippocampal slices. Adenosine and ATP had inhibitory actions that could be prevented by the P1-receptor blocker 8-phenyltheophylline. 3. The stable nucleotides had no consistent effects on the firing rate of single neurones in stratum pyramidale of the CA1 region, although adenosine and ATP produced a xanthine-sensitive inhibition. 4. Adenosine selectively reduced the sensitivity of CA1 neurones to microiontophoretically applied carbachol whereas stable nucleotides did not. 5. It is concluded that there are neither P2x- nor P2y-receptors for adenine nucleotides on rat hippocampal CA1 pyramidal cells at the Schaffer collateral and commissural terminals in stratum radiatum.