Post-inhibitory excitation of adenosine on neurotransmission in guinea pig hippocampal slices.
The postsynaptic field potential (population spike potential; PS) was recorded from the granule cell layer of guinea pig hippocampal slices. Adenosine at low concentrations ranging from 10 nM to 1 microM enhanced the amplitude of PS, whereas at concentrations over 10 microM it inhibited the neurotransmission. There appeared to be a rebound phenomenon after the removal of adenosine at inhibitory concentrations and the amplitude of the PS overshot the initial amplitude (we called this post-inhibitory excitation; PIE). Neither depressants such as gamma-aminobutyric acid (GABA; 1 mM) nor sodium pentobarbital (100 microM) by itself induced PIE. After application of GABA or sodium pentobarbital together with adenosine (0.1 microM), however, removal of all agents could induce the PIE. PIE as well as the excitatory effect of adenosine at low concentrations was counteracted by application of H-7 (100 microM), melittin or polymyxin B, potent protein kinase C (PKC) inhibitors, suggesting that the excitatory effect of adenosine is mediated by a metabolic process involving PKC. These results indicate that PIE induced by adenosine at high concentrations is due to a mechanism similar to the excitatory effect induced by adenosine at low concentrations, and that during application of adenosine at high concentrations the excitation is masked by its potent inhibitory effect.
Nishimura
S
S
Department of Physiology, School of Medicine, Kobe University, Japan.
Okada
Y
Y
Amatsu
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000227:Adenine Nucleotides / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000227:Adenine Nucleotides; D007546:Isoquinolines; D010879:Piperazines; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D010424:Pentobarbital; D000241:Adenosine