Adenosine antagonists increase spontaneous and evoked transmitter release from neuronal cells in culture.
To examine the role played by endogenous adenosine in the modulation of transmitter release in the CNS, the effect of adenosine antagonists has been studied. Two systems have been used: EPSPs recorded from pyramidal cells in organotypic hippocampal cultures; and release of newly synthesized [3H]glutamate from cerebellar granule cells in dissociated culture. Bath application of 0.1-1 microM 8-phenyltheophylline (8-PT) reversibly increased both the number and size of spontaneous EPSPs and caused bursting activity in some cells. This effect was blocked by the glutamate antagonist gamma-D-glutamylglycine (DGG) (1 mM) but not by atropine (10 microM) or bicuculline (100 microM). Another adenosine antagonist isobutylmethylxanthine (IBMX, 10 microM) had a similar effect to 8-PT. Spontaneous activity in pyramidal cells and that induced by adenosine antagonists was blocked by the adenosine agonist 2-chloroadenosine (2-CA) (0.2-20 microM). 8-PT (10 microM) markedly potentiated K+-stimulated release of newly synthesized glutamate, and also enhanced basal glutamate release. The agonist (-)-phenylisopropyladenosine ((-)-PIA, 2 microM) which is relatively selective for A1 receptors, reduced by 19 +/- 5% the 8-PT-induced enhancement, and reduced K+-stimulated glutamate release in the absence of 8-PT to a similar extent. In contrast 5'-N-ethylcarboxamido adenosine (NECA, 2 microM), which is a relatively selective A2 agonist, slightly enhanced glutamate release. From these results it is likely that 8-PT potentiates glutamate release in both systems by blocking the effect of endogenous adenosine on presynaptic A1 receptors.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009928:Organ Specificity; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D005971:Glutamates; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D000241:Adenosine