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.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D005033:Ethylmaleimide / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011983:Receptors, Purinergic; D020889:Rolipram
D005971:Glutamates; D011760:Pyrrolidinones; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D005576:Colforsin; D010660:Phenylisopropyladenosine; D018698:Glutamic Acid; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D020889:Rolipram; D005033:Ethylmaleimide