Presynaptic adenosine A2 and N-methyl-D-aspartate receptors regulate dopamine synthesis in rat striatal synaptosomes.
Dopamine synthesis rate and cyclic AMP concentration were measured in synaptosomes prepared from rat striatum. Dopamine synthesis rate was decreased by the addition of either adenosine deaminase or 8-phenyltheophylline, an adenosine receptor blocker, and was increased by the addition of 2-chloroadenosine. The addition of L-glutamate in the absence of adenosine deaminase decreased both dopamine synthesis rate and cyclic AMP concentration; in the presence of adenosine deaminase, glutamate had no effect on basal dopamine synthesis, but enhanced K(+)-stimulated synthesis. Both these effects of glutamate were abolished in Ca2(+)-free medium or in the presence of 2-amino-5-phosphonovalerate, an N-methyl-D-aspartate (NMDA) receptor blocker. In Mg2(+)-free medium with adenosine deaminase, glutamate enhanced both basal and K(+)-stimulated synthesis. These results suggest that dopaminergic terminals have A2 adenosine receptors, whose activation can stimulate dopamine synthesis by a cyclic AMP-dependent mechanism, and NMDA receptors, which modulate dopamine synthesis by a Ca2(+)-dependent mechanism.
Chowdhury
M
M
University Laboratory of Physiology, Oxford, England.
Fillenz
M
M
D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000648:ultrastructure; D003470:Culture Media; D004298:Dopamine / Q000096:biosynthesis*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D003470:Culture Media; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D011983:Receptors, Purinergic; D018698:Glutamic Acid; D000243:Adenosine Deaminase; D000241:Adenosine; D004298:Dopamine