Effects of N-ethylmaleimide and forskolin on glutamate release from rat hippocampal slices. Evidence that prejunctional adenosine receptors are linked to N-proteins, but not to adenylate cyclase.

In the present experiments we have examined the effect of N-ethylmaleimide (NEM) on the release of [3H]glutamate from rat hippocampal slices. Pretreatment of slices with NEM in a concentration between 50 microM and 200 microM, can inhibit the GTP-binding protein (Ni) that transmits receptor signals into inhibitions of adenylate cyclase, without affecting the Ns-protein, that transmits signals into stimulation of the cyclase, or the cyclase. The adenosine receptor agonist R-phenylisopropyladenosine (R-PIA, 1 microM) caused an approximately 50% inhibition of the evoked [3H]glutamate release. This effect was completely prevented by NEM treatment, which did not affect basal or stimulated release of the amino acid. By contrast, the effect of R-PIA was unaffected by adding an adenylate cyclase stimulator (forskolin 1 microM) and a phosphodiesterase inhibitor (rolipram, ZK 62.711, 30 microM) which raised the cyclic AMP content of the slices approximately 10-fold. In conclusion, these results suggest that the adenosine receptor that mediates prejunctional inhibition of glutamate release is coupled to a protein similar to the Ni-protein, but that another effector than adenylate cyclase is involved.