Excitatory effect of propentofylline on neurotransmission in guinea pig hippocampal slice

The postsynaptic field potential (population spike; PS) was recorded from the granule cell layer of guinea pig hippocampal slices after electrical stimulation of the perforant path. Propentofylline, a xanthine derivative, enhanced the amplitude of PS to 120-150% of the original level at a concentration range of 100 nM to 1 mM. Theophylline at concentrations over 10 microM increased the PS amplitude to 200% of the original amplitude. Simultaneous application of 1-(5-isoquin-olinesulfonyl)-2-methylpiperazine dihydrochloride (H-7; 100 microM), a protein kinase C (PKC) inhibitor, significantly blocked the excitatory effect of propentofylline, but it failed to counteract the excitatory effect of theophylline. These results indicate that the excitatory effect of propentofylline is mediated by a metabolic process involving PKC and that the protective effect of propentofylline on neuronal damage caused by hypoxia is not due to the inhibition of synaptic transmission.