title: Adenosine antagonists increase spontaneous and evoked transmitter release from neuronal cells in culture.
abstract: 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.
mesh_terms: 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*
chemical_list: D005971:Glutamates; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D000241:Adenosine