Premium
Interacting Presynaptic k ‐Opioid and GABA A Receptors Modulate Dopamine Release from Rat Striatal Synaptosomes
Author(s) -
Ronken E.,
Mulder A. H.,
Schoffelmeer A. N. M.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb09797.x
Subject(s) - dopaminergic , chemistry , dopamine , bicuculline , agonist , medicine , kainate receptor , dopamine receptor , d2 like receptor , endocrinology , gabaa receptor , pharmacology , dopamine receptor d1 , receptor , biology , glutamate receptor , biochemistry , ampa receptor
— 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 D 2 autoreceptors, calcium‐dependent K + ‐stimulated [ 3 H]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 (EC 50 0.2 n M ) and its antagonism by norbinaltorphimine. Neither μ‐nor δ‐selective receptor agonists affected release of [ 3 H]‐dopamine. In addition, GABA potently inhibited the evoked [ 3 H]dopamine release (EC 50 0.4 n M ) through activation of GABA A 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 GABA B 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 D 2 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 [ 3 H]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.