Differential effect of quinpirole and 7-OH-DPAT on the spontaneous [3H]-dopamine efflux from rat striatal synaptosomes

Alicia García-Sanz, Albert Badia, M. Victoria Clos

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Abstract

The effect of quinpirole and 7-OH-DAPT, two D2-like agonists, were examined using superfused rat striatal synaptosomes to study the autoregulation of spontaneous [3H]-dopamine ([3H]-DA) release. Basal [3H]-DA efflux was Ca2+-dependent by ∼45% and was inhibited by cadmium 10 μM by 24%. Quinpirole (1 nM to 3 μM) inhibited spontaneous [3H]-DA efflux in a concentration-dependent manner (pEC50 = 7.56 ± 0.07 and Emax = 26 ± 0.09%) and this effect was competitively antagonized by haloperidol (0.3-1 nM) (apparent pA2 = 9.61 ± 0.08). In addition, activation of the D2 DA autoreceptor by quinpirole only modulates the calcium-dependent component of [3H]-DA efflux. Low concentrations of a putative-selective D3 DA agonist, (±)-7-OH-DPAT (0.03-0.1 μM), inhibited spontaneous [3H]-DA release by 13% (P < 0.05), but higher drug concentrations (≥1 μM) increased basal [3H]-DA efflux in a concentration-dependent, nonsaturable, but reversible manner. Haloperidol (1-10 nM) reversed the (±)-7-OH-DPAT-induced inhibition, but not the increase in [3H]-DA outflow. The effect of (±)-7-OH-DPAT was mimicked by (+)-7-OH-DPAT. However, another putative D3 DA agonist, PD 128,907 (1 nM to 3 μM), decreased spontaneous tritium efflux (maximal inhibition of 19 ± 3.06% at 3 μM, P < 0.01). The effect of 7-OH-DPAT 10 μM was independent of the presence of extracellular Ca2+, since its effect on basal [3H]-DA outflow was not significantly modified in a 200 nM free-Ca2+ medium. In addition, the 7-OH-DPAT-induced enhancement of basal [3H]-DA efflux does not involve depolarization of nerve terminals or the reversal of the DA uptake system, as tetrodotoxin (1 μM) and nomifensine (1 μM) did not modify the effect of 7-OH-DPAT 10 μM. The present data indicate that activation of D2 DA autoreceptor subtype by quinpirole inhibits Ca2+-dependent spontaneous [3H]-DA efflux. 7-OH-DPAT activates the D2 DA autoreceptor at low concentrations, whereas its action in releasing [3H]-DA effect is not receptor-mediated and could involve other mechanisms other than either conventional vesicular exocytosis or the DA uptake system. © 2001 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)65-73
JournalSynapse
Volume40
Issue number1
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • Presynaptic dopamine autoreceptors
  • Spontaneous [ H]-dopamine release 3
  • Striatum
  • Synaptosomes

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