Dopamine receptor regulation of Ca2+ levels in individual isolated nerve terminals from rat striatum: comparison of presynaptic D1-like and D2-like receptors.
We have directly observed the effects of activating presynaptic D1-like and D2-like dopamine receptors on Ca2+ levels in isolated nerve terminals (synaptosomes) from rat striatum. R-(+)-SKF81297, a selective D1-like receptor agonist, and (-)-quinpirole, a selective D2-like receptor agonist, induced increases in Ca2+ levels in different subsets of individual striatal synaptosomes. The SKF81297- and quinpirole-induced effects were blocked by R-(+)-SCH23390, a D1-like receptor antagonist, and (-)-sulpiride, a D2-like receptor antagonist, respectively. SKF81297- or quinpirole-induced Ca2+ increases were inhibited following blockade of voltage-gated calcium channels or sodium channels. In a larger subset of synaptosomes, quinpirole decreased baseline Ca2+. Quinpirole also inhibited veratridine-induced increases in intrasynaptosomal Ca2+ level. Immunostaining confirmed the presynaptic expression of D1, D5, D2 and D3 receptors, but not D4 receptors. The array of neurotransmitter phenotypes of the striatal nerve endings expressing D1, D5, D2 or D3 varied for each receptor subtype. These results suggest that presynaptic D1-like and D2-like receptors induce increases in Ca2+ levels in different subsets of nerve terminals via Na+ channel-mediated membrane depolarization, which, in turn, induces the opening of voltage-gated calcium channels. D2-like receptors also reduce nerve terminal Ca2+ in a different but larger subset of synaptosomes, consistent with the predominant presynaptic action of dopamine in the striatum being inhibitory.
Wu
Jianlin
J
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
Dougherty
John J
JJ
Nichols
Robert A
RA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018377:Neurotransmitter Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017661:Receptors, Presynaptic; D015222:Sodium Channels; D019257:Quinpirole; D014701:Veratridine; D002118:Calcium