Activation of D1 dopamine receptors stimulates the release of GABA in the basal ganglia

Department of Physiology, Biophysics and Neurosciences, Instituto Politecnico Nacional, Mexico, D.F.
Neuroscience Letters (Impact Factor: 2.03). 09/1990; 116(1-2):136-40. DOI: 10.1016/0304-3940(90)90399-T
Source: PubMed


Here we have explored whether dopamine is able to modulate the release of gamma-aminobutyric acid (GABA) from striatal terminals to substantia nigra pars reticulata, entopeduncular nucleus, globus pallidus and caudate-putamen. The type of dopamine receptors involved was assessed by the blocking effect of either SCH 23390 (D1 antagonist) or (-)-sulpiride (D2 antagonist) of the dopamine effect. Dopamine stimulated (EC50 3.2 microM) the depolarization-induced release of [3H]GABA from slices isolated from all of the above mentioned nuclei. SCH 23390 dose-dependently blocked the dopamine stimulation, but (-)-sulpiride did not show any blocking effect. The results suggest that dopamine via D1 receptors modulates the release of GABA from striatal GABAergic terminals.

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    • "GABA release by these projections is modulated by separate dopamine receptors. In pallidonigral terminals dopamine D4Rs regulate GABA release (Acosta-García et al., 2009; de Jesus Aceves et al., 2011) while in striatonigral projections D1Rs modulate release (Florán et al., 1990; Radnikow and Misgeld, 1998). "
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    ABSTRACT: In striatonigral projections activation of dopamine D3 receptors (D3Rs) potentiates the stimulation of GABA release and cAMP production caused by activation of dopamine D1 receptors (D1Rs). Cytoplasmic [Ca(2+)] in the terminals controls this response by modulating CaMKII, an enzyme that depresses D3R action. To examine the effects of dopamine deprivation on D3R signaling we investigated their function in striatonigral terminals of hemiparkinsonian rats. Denervation switched the signaling cascade initiated by D3R activation. In the non-lesioned side activation of D3R potentiated the stimulatory effects of D1R activation on cAMP production and K(+)-depolarization induced [(3)H] GABA release. In contrast, in the denervated side the stimulatory effects of both D1R activation and forskolin administration were blocked by D3R activation. In non-lesioned slices, D3R responses were inhibited by the activation of CaMKII produced by K(+)-depolarization (via increased Ca(2+) entry). The CaMKII-induced inhibition was blocked by the selective inhibitor KN-62. In denervated tissues the response to D3R stimulation was not modified either by K(+) depolarization or by blocking CaMKII with KN-62. Immunoblotting studies showed that depolarization-induced CaMKII binding to the D3 receptor and CaMKII phosphorylation were suppressed in denervated tissues. We also determined calmodulin expression with PCR and immunoblot techniques. Both techniques showed that calmodulin expression was depressed in the lesioned side. In sum, our studies show that dopaminergic denervation switches the D3R signaling cascade and depresses CaMKII signaling through a process that appears to involve reduced calmodulin levels. Since calmodulin is a major cytoplasmic Ca(2+) buffer our findings suggest that abnormal Ca(2+) buffering may be an important component of the abnormalities observed during dopaminergic denervation. Copyright © 2014. Published by Elsevier Inc.
    Neurobiology of Disease 12/2014; 74. DOI:10.1016/j.nbd.2014.12.008 · 5.08 Impact Factor
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    • "In striatonigral projections activation of D1Rs stimulates GABA release (Floran et al., 1990; Radnikow and Misgeld, 1998; Nava-Asbell et al., 2007; Acosta-Garcia et al., 2009). In striatopallidal terminals dopamine activates D2Rs that depress GABA release (Floran et al., 1997; Cooper and Stanford, 2001). "
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    ABSTRACT: Modulation of L-type Ca2+-channel function by dopamine is a major determinant of the rate of action potential firing by striatal medium spiny neurons. However, the role of these channels in modulating GABA release by nerve terminals in the basal ganglia is unknown. We found that depolarization-induced [3H]GABA release in both the substantia nigra reticulata and the external globus pallidus (GPe), was depressed by about 50% by either the selective L-channel dihydropyridine blocker nifedipine or the P/Q channel blocker ω-agatoxin TK. The effects of these blockers were additive and together eliminated about 90% of depolarization-induced [3H]GABA release. In addition, in the substantia nigra reticulata, dihydropyridines prevented both the stimulation of [3H]GABA release produced by dopamine D1 receptor activation and the inhibition caused by D4 receptor activation. In the GP nifedipine blocked the effects of D2 and A2A receptor coactivation as well as the effects of activating adenylyl cyclase with forskolin. ω-Agatoxin TK did not interfere with the action of these modulatory agents. The L-type Ca2+-channel agonist BAYK 8644 stimulated GABA release in both substantia nigra reticulata and GP. Because dihydropyridine sensitivity is a key criterion to identify L-type Ca2+-channel activity, our results imply that these channels are determinant of GABA release modulation by dopamine in striatonigral, striatopallidal and pallidonigral terminals.
    Neuroscience 01/2014; 256:292–301. DOI:10.1016/j.neuroscience.2013.10.037 · 3.36 Impact Factor
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    • "Two families of receptors mediate the action of dopamine through the basal ganglia, D1-like (D 1 and D 5 subtypes) and D2-like (D 2short , D 2long D 3 and D 4 subtypes). D1-like receptors are expressed predominantly in substance P/Dynorphyn positive MNSs GABAergic neurons and their activation increases the firing rate at soma and also the GABA release in the termi‐ nals [19] [20] [21] [22]. It have been reported that some population of striato-nigral neurons also ex‐ presses D 3 receptors [14] [23]. "

    01/2014; INTECH.
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