D1-like dopamine receptors regulate GABAA receptor function to  modulate hippocampal neural progenitor cell proliferation.
The proliferation and differentiation of neural progenitor (NP) cells can be regulated by neurotransmitters including GABA and dopamine. The present study aimed to examine how these two neurotransmitter systems interact to affect post-natal hippocampal NP cell proliferation in vitro. Mouse hippocampal NP cells express functional GABAA receptors, which upon activation led to an increase in intracellular calcium levels via the opening of L-type calcium channels. Activation of these GABAA receptors also caused a significant decrease in proliferation; an effect that required the entry of calcium through L-type calcium channels. Furthermore, while activation of D1-like dopamine receptors had no effect on proliferation, it abrogated the suppressive effects of GABAA receptor activation on proliferation. The effects of D1-like dopamine receptors are associated with a decrease in the ability of GABAA receptors to increase intracellular calcium levels, and a reduction in the surface expression of GABAA receptors. In this way, D1-like dopamine receptor activation can increase the proliferation of NP cells by preventing GABAA receptor-mediated inhibition of proliferation. These results suggest that, in conditions where NP cell proliferation is under the tonic suppression of GABA, agonists which act through D1-like dopamine receptors may increase the proliferation of neural progenitors.
Goffin
Darren
D
Department of Neurodegeneration Research, Neurology CEDD, GlaxoSmithKline, Essex, UK.
Aarum
Johan
J
Schroeder
Jörn E
JE
Jovanovic
Jasmina N
JN
Chuang
Tsu Tshen
TT
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018682:GABA Agents / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015259:Dopamine Agents; D018682:GABA Agents; D011724:Pyridazines; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D009118:Muscimol; C049853:gabazine; D001973:Bromodeoxyuridine; D009543:Nifedipine; D002118:Calcium