Interacting Presynaptic k-Opioid and GABAA Receptors Modulate Dopamine Release from Rat Striatal Synaptosomes |
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Authors: | E. Ronken A. H. Mulder A. N. M. Schoffelmeer |
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Affiliation: | Department of Pharmacology, Faculty of Medicine, Research Institute Neurosciences Vrije Universiteit, Amsterdam, The Netherlands |
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Abstract: | Abstract— The presynaptic regulation of stimulated dopa-mine release from superfused rat striatal synaptosomes by opioids and γ-aminobutyric acid (GABA) was studied. It was found that in addition to dopamine D2 autoreceptors, calcium-dependent K+-stimulated [3H]dopamine release was inhibited through activation of a homogeneous population of k -opioid receptors in view of the potent inhibitory effect of the k -selective agonist U69.593 (EC50 0.2 nM) and its antagonism by norbinaltorphimine. Neither μ-nor δ-selective receptor agonists affected release of [3H]-dopamine. In addition, GABA potently inhibited the evoked [3H]dopamine release (EC50 0.4 nM) through activation of GABAA receptors in view of the GABA-mimicking effect of muscimol, the sensitivity of its inhibitory effect to picro-toxin and bicuculline, and the absence of an effect of the GABAB receptor agonist baclofen. In the presence of a maximally effective concentration of GABA, U69,593 did not induce an additional release-inhibitory effect, indicating that these receptors and the presynaptic D2 receptor are colocalized on the striatal dopaminergic nerve terminals. The excitatory amino acid agonists N-methyl-d -aspartate and kainate, as well as the cholinergic agonist carbachol, stimulated [3H]dopamine release, which was subject to k -opioid receptor-mediated inhibition. In conclusion, striatal dopamine release is under regulatory control of multiple excitatory and inhibitory neurotransmitter by activation of colocalized presynaptic receptors for excitatory amino acids, acetylcholine, dopamine, dynorphins, and GABA within the dopaminergic nerve terminals. Together, these receptors locally control ongoing dopamine neurotransmission. |
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Keywords: | Dopamine release—k-Opioid receptor ABAA receptor triatal synaptosome xcitatory amino acid opamine D2 autoreceptors |
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