Dopamine induces a biphasic modulation of hypothalamic ANF neurons: a ligand concentration-dependent effect involving D5 and D2 receptor interaction.
Increasing evidence now suggests that more than one subtype of dopamine receptors is co-expressed in some of the central neurons. The neurobiological effects on the host cells when these receptors are concurrently activated by their common physiological ligand, dopamine, however, remains elusive. Among the members of the family of dopamine receptors, coupling of D1-like dopamine receptors to Gs and D2-like receptors to Gi proteins are known to augment or suppress cellular functions respectively, through modulation of adenylyl cyclase activity and consequently cAMP generation. Simultaneous activation of D1 and D2 receptors in transfected cell lines expressing the two cloned receptors, however, produced antagonistic effects. This is in contrast to in vivo studies, in which concurrent activation of D1-like and D2-like receptors by their respective agonists may induce synergistic or antagonistic effects or both. We report here that in long-term rat hypothalamic cell cultures, activation of both D1-like (D1 and D5) and D2 receptors on atrial natriuretic factor-producing neurons by dopamine yields a biphasic response. The response is ligand concentration-dependent and involves type II adenylyl cyclases. This process is mediated primarily through antagonistic and synergistic interactions of D5 and D2 receptors as the event is mimicked by the concurrent activation of these two receptors co-transfected in CHO cells. Our present findings suggest a novel action of dopamine, and the biochemical processes involved may underlie some of the pharmacological actions of atypical anti-psychotic drugs. Molecular Psychiatry (2000) 5, 39-48.
Lee
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Cell Biology Laboratory, Division of Molecular Schizophrenia, Mental Health Research Institute of Victoria, Parkville, Australia 3052.
Huang
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Lim
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D009320:Atrial Natriuretic Factor / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D016466:CHO Cells; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D010455:Peptides; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D050641:Receptors, Dopamine D5; D013194:Staining and Labeling; D014862:Wasp Venoms / Q000494:pharmacology
D000906:Antibodies; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014862:Wasp Venoms; D050641:Receptors, Dopamine D5; D005576:Colforsin; D019257:Quinpirole; D003994:Bucladesine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C037500:mastoparan; D009320:Atrial Natriuretic Factor; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine