Dopamine receptor regulation of Ca levels in individual isolated nerve terminals from rat striatum: Comparison of presynaptic D 1-like and D2-like receptors

We have directly observed the effects of activating presynaptic D-1-like and D-2-like dopamine receptors on Ca2+ levels in isolated nerve terminals (synaptosomes) from rat striatum. R-(+)-SKF81297, a selective D-1-like receptor agonist, and (-)-quinpirole, a selective D-2-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 D-1-like receptor antagonist, and (-)-sulpiride, a D-2-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 D-1, D-5, D-2 and D-3 receptors, but not D-4 receptors. The array of neurotransmitter phenotypes of the striatal nerve endings expressing D-1, D-5, D-2 or D-3 varied for each receptor subtype. These results suggest that presynaptic D-1-like and D-2-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. D-2-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.