Opposite presynaptic regulations by glutamate through NMDA receptors of dopamine synthesis and release in rat striatal synaptosomes.
Purified striatal synaptosomes were superfused continuously with L-[3,5-3H]tyrosine to measure simultaneously the synthesis ([3H]water formed during the conversion of [3H]tyrosine into [3H]DOPA) and the release of [3H]dopamine ([3H]DA). Glutamate (10(-3) M) and NMDA (10(-3) M, in the absence of Mg2+) stimulated the release of [3H]DA, but they reduced the efflux of [3H]water. This reduction of [3H]DA synthesis was blocked by 2-amino-5-phosphonovalerate indicating the involvement of NMDA receptors. Although D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) and kainate stimulated the release of [3H]DA, they did not affect its synthesis. The glutamate-evoked inhibition of [3H]DA synthesis was prevented when synaptosomes were superfused continuously with adenosine deaminase plus quinpirole, a treatment which markedly reduces the phosphorylation of tyrosine hydroxylase by cAMP dependent protein kinase. The opposite effects of glutamate on [3H]DA synthesis and release were mimicked by ionomycin (10(-6) M). It is proposed that both an activation of a cyclic nucleotide phosphodiesterase and a dephosphorylation of tyrosine hydroxylase linked to the influx of calcium through NMDA receptors is responsible for the inhibition of dopamine synthesis by glutamate and that calcineurin could play a critical role in these processes.
Desce
J M
JM
INSERM U 114, Collège de France, Chaire de Neuropharmacologie, Paris.
Godeheu
G
G
Galli
T
T
Glowinski
J
J
Chéramy
A
A
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology / Q000502:physiology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D015259:Dopamine Agents; D004873:Ergolines; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D019257:Quinpirole; D015124:8-Bromo Cyclic Adenosine Monophosphate; D018698:Glutamic Acid; D014443:Tyrosine; D015759:Ionomycin; D000243:Adenosine Deaminase; D004298:Dopamine