Nicotinamide adenine dinucleotides mimic adenosine inhibition on synaptic transmission by decreasing glutamate release in rat hippocampal slices.
To assess the possible inhibitory action of nicotinamide adenine dinucleotides on the synaptic release of glutamate, electrophysiological and biochemical experiments were performed on rat hippocampal slices. Perfusion of adenosine, beta-nicotinamide adenine dinucleotide (NAD) or beta-nicotinamide adenine dinucleotide phosphate (NADP), reversibly inhibited the field excitatory postsynaptic potentials (fEPSP). Dose-response curves for their inhibitory action showed that these three substances had a similar potency in the range of concentrations from 0.1 microM to 100 microM. NADP and adenosine (100 microM) halved the K(+)-induced release of endogenous glutamate and aspartate, leaving gamma-amino-butyric acid (GABA) levels unchanged. 3-Isobutyl-1-methylxanthine (IBMX) 200 microM, an antagonist of the P1-purinoreceptors, antagonized the depressant effects of these coenzymes on both fEPSP and also on amino acid release. Based on these results we propose that nicotinamide adenine dinucleotides, similar to adenosine, inhibit excitatory synaptic transmission in the rat hippocampus by decreasing glutamate release from synaptic terminals.
Galarreta
M
M
Departamento de Investigación, Hospital Ramón y Cajal, INSALUD, Madrid, Spain.
Solís
J M
JM
Menéndez
N
N
Conejero
C
C
Martín del Río
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009243:NAD / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D000596:Amino Acids; D005971:Glutamates; D018047:Receptors, Purinergic P1; D009243:NAD; D018698:Glutamic Acid; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine