Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons.
Despite the importance of dopamine signaling, it remains unknown if the two major subclasses of dopamine receptors exist on the same or distinct populations of neurons. Here we used confocal microscopy to demonstrate that virtually all striatal neurons, both in vitro and in vivo, contained dopamine receptors of both classes. We also provide functional evidence for such colocalization: in essentially all neurons examined, fenoldopam, an agonist of the D1 subclass of receptors, inhibited both the Na+/K+ pump and tetrodotoxin (TTX)-sensitive sodium channels, and quinpirole, an agonist of the D2 subclass of receptors, activated TTX-sensitive sodium channels. Thus D1 and D2 classes of ligands may functionally interact in virtually all dopamine-responsive neurons within the basal ganglia.
Aizman
O
O
Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Q2:09, 171 76 Stockholm, Sweden.
Brismar
H
H
Uhlén
P
P
Zettergren
E
E
Levey
A I
AI
Forssberg
H
H
Greengard
P
P
Aperia
A
A
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D065127:Dopamine D2 Receptor Antagonists; D018818:Fenoldopam / Q000494:pharmacology; D018613:Microscopy, Confocal; D017072:Neostriatum / Q000737:chemistry / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000032:analysis / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019257:Quinpirole; D013779:Tetrodotoxin; D013469:Sulpiride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D018818:Fenoldopam