Expression of D2 receptor isoforms in cultured neurons reveals equipotent autoreceptor function.
Alternative splicing of the dopamine D2 receptor gene produces two distinct isoforms referred to as D2long (D2L) and D2short (D2S). In mesencephalic dopamine neurons, inhibition of the firing rate through activation of somatodendritic D2 receptors and blockade of neurotransmitter release through stimulation of terminal D2 receptors represent major roles of D2 autoreceptors. Recently, data obtained from D2L-deficient mice suggested that D2S acts as the preferential D2 autoreceptor. In the present study, we investigate whether this D2 isoform-specific autoreceptor function is linked to differences in the subcellular localization and/or signaling properties of the D2S and D2L using mesencephalic neurons transfected with enhanced green fluorescent protein (EGFP)-tagged receptors. Our results show that EGFP-tagged D2S and D2L are localized to the axonal and somatodendritic compartments of mesencephalic neurons. In addition, we demonstrate that EGFP-tagged D2S and D2L regulate cellular excitability, neurotransmitter release and basal levels of intracellular calcium with similar effectiveness. Overall, our morphological and electrophysiological studies suggest that the major D2 autoreceptor function attributed to D2S is likely explained by the predominant expression of this isoform in dopamine neurons rather than by distinct subcellular localization and signaling properties of D2S and D2L.
Jomphe
Claudia
C
Department of Pharmacology, Center for Research in Neurological Sciences, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, QC, Canada H3C 3J7.
Tiberi
Mario
M
Trudeau
Louis-Eric
LE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008636:Mesencephalon / Q000166:cytology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection / Q000379:methods
D017660:Autoreceptors; D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D019257:Quinpirole; D002118:Calcium