Dopamine receptor subtypes colocalize in rat striatonigral neurons.
Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1 dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+ current. The D2 agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+ currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in whole-cell recordings, whereas quinpirole consistently (6/10) enhanced currents--suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3 receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3 receptors.
Surmeier
D J
DJ
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163.
Eberwine
J
J
Wilson
C J
CJ
Cao
Y
Y
Stefani
A
A
Kitai
S T
ST
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D015139:Blotting, Southern; D001971:Bromocriptine / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004873:Ergolines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009838:Oligodeoxyribonucleotides; D019257:Quinpirole; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011954:Receptors, Dopamine / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*
D016375:Antisense Elements (Genetics); C493595:Drd3 protein, rat; D004873:Ergolines; D009838:Oligodeoxyribonucleotides; D015347:RNA Probes; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015222:Sodium Channels; D019257:Quinpirole; D001971:Bromocriptine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004247:DNA