Regulation of Glutamate and Aspartate Release from Slices of the Hippocampal CA1 Area: Effects of Adenosine and Baclofen

Abstract

Glutamate and/or aspartate is the probable transmitter released from synaptic terminals of the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers in area CA1 of the rat hippocampal formation. Slices of the CA1 area were employed to test the effects of adenosine- and gamma-aminobutyrate (GABA)-related compounds on the release of glutamate and aspartate from this projection. Under the conditions of these experiments, the release of glutamate and aspartate evoked by 50 mM K+ was more than 90% Ca2+-dependent and originated predominantly from the CA3-derived pathways. Adenosine reduced the K+-evoked release of glutamate and aspartate by a maximum of about 60%, but did not affect the release of GABA. This action was reversed by 1 microM 8-phenyltheophylline. The order of potency for adenosine analogues was as follows: L-N6-phenylisopropyladenosine greater than N6-cyclohexyladenosine greater than D-N6-phenylisopropyladenosine approximately equal to 2-chloroadenosine greater than adenosine much greater than 5'-N-ethylcarboxamidoadenosine. 8-Phenyltheophylline (10 microM) by itself enhanced glutamate/aspartate release, whereas dipyridamole alone depressed release. These results support the view that adenosine inhibits transmission at Schaffer collateral-commissural-ipsilateral associational synapses mainly by reducing transmitter release and that these effects involve the activation of an A1 receptor. Neither adenosine, L-N6-phenylisopropyladenosine, nor 8-phenyltheophylline affected the release of glutamate or aspartate evoked by 10 microM veratridine. The differing effects of adenosine compounds on release evoked by K+ and veratridine suggest that A1 receptor activation either inhibits Ca2+ influx through the voltage-sensitive channels or interferes with a step subsequent to Ca2+ entry that is coupled to the voltage-sensitive Ca2+ channels in an obligatory fashion. Neither baclofen nor any other agent active at GABAB or GABAA receptors affected glutamate or aspartate release evoked by elevated K+ or veratridine. Therefore, either baclofen does not inhibit transmission at these synapses by depressing transmitter release or else it does so in a way that cannot be detected when a chemical depolarizing agent is employed.

NMDA receptor-mediated extracellular adenosine accumulation is blocked by phosphatase 1/2A inhibitors

“…Its action is mediated by adenosine A 1 , A 2A , A 2B , and A 3 receptors. Adenosine modulates neuronal excitability by decreasing neuronal firing [50] and inhibiting the release of neurotransmitters, such as glutamate [4,17], aspartate [6], acetylcholine [34], and γ-aminobutyric acid [3,7]. These effects are mediated by activation of presynaptic adenosine A1 receptors.…”

Reduced aspartate release from rat hippocampal synaptosomes loaded with Clostridial toxin light chain by electroporation: Evidence for an exocytotic mechanism

“…In those pathways, aspartate immunoreactivity was associated with synaptic vesicles to the same degree as glutamate or GABA immunoreactivity. Aspartate is coreleased with glutamate from the Schaffer collateral-commissural and dentate gyrus associationalcommissural pathways in a Ca 2+ -dependent manner [2,3,19] and could serve as a co-transmitter through its selective activation of NMDA receptors [4,22]. However, the mechanism of aspartate release appears to differ in some respects from that of the recognized amino acid transmitters.…”

Beta-adrenergic receptor-mediated regulation of extracellular adenosine in cerebral cortex in culture

“…Adenosine receptors in the CNS have been well characterized in ligand binding studies and have been mapped by autoradiography (Bruns et al, 1980;Goodman et al, 1983). Biochemical experiments have shown that adenosine blocks release of glutamate and aspartate from a number of preparations (Dolphin and Archer, 1983;Corradetti et al, 1984;Fastbom and Fredholm, 1985;Burke and Nadler, 1988), while electrophysiological experiments have shown that adenosine blocks excitatory postsynaptic events (Schubert and Mitzdorf, 1979;Dunwiddie, 1984;Okada and Ozawa, 199 1;Scholz and Miller, 199 1;Yoon and Rothman, 199 1). Adenosine appears to block transmitter release by a presynaptic action limiting calcium influx (Wu et al, 1982;Proctor and Dunwiddie, 1983;Madison et al, 1987;Fredholm and Dunwiddie, 1988), and considerable evidence has been gathered showing that adenosine blocks calcium currents in peripheral (Dolphin et al, 1986;MacDonald et al, 1986) and central neurons (Proctor and Dunwiddie, 1983).…”