Dopamine D3 receptor-preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal-regulated kinase phosphorylation

Autor:	PierFranco Spano, Silvia Zanetti, C. Missale, Ginetta Collo
Rok vydání:	2008
Předmět:	medicine.medical_specialty Quinpirole Tetrahydronaphthalenes Tyrosine 3-Monooxygenase Dopamine Neurogenesis Biology chemistry.chemical_compound Mice Dopamine receptor D3 Neurotrophic factors Mesencephalon Internal medicine medicine Animals Nerve Growth Factors Enzyme Inhibitors Extracellular Signal-Regulated MAP Kinases Cell Shape Cells Cultured 7-OH-DPAT Tyrosine hydroxylase Dose-Response Relationship Drug Receptors Dopamine D2 General Neuroscience Dopaminergic Receptors Dopamine D3 Dendrites Substantia Nigra Amphetamine Dopamine D2 Receptor Antagonists Endocrinology chemistry Dopamine Agonists Dopamine Antagonists Indirect agonist medicine.drug
Zdroj:	The European journal of neuroscience. 28(7)
ISSN:	1460-9568
Popis:	Clinical improvements in Parkinson's disease produced by dopamine D3 receptor-preferring agonists have been related to their neuroprotective actions and, more recently, to their neuroregenerative properties. However, it is unclear whether dopamine agonists produce their neurotrophic effects by acting directly on receptors expressed by the mesencephalic dopaminergic neurons or indirectly on receptors expressed by astrocytes, via release of neurotrophic factors. In this study, we investigated the effects of the dopamine D3 receptor-preferring agonists quinpirole and 7-hydroxy-N,N-di-propyl-2-aminotetralin (7-OH-DPAT), as well as of the indirect agonist amphetamine, on dopaminergic neurons identified by tyrosine hydroxylase immunoreactivity (TH-IR). Experiments were performed on neuronal-enriched primary cultures containing less than 0.5% of astrocytes prepared from the mouse embryo mesencephalon. After 3 days of incubation, both quinpirole (1-10 microm) and 7-OH-DPAT (5-500 nm) dose-dependently increased the maximal dendrite length (P < 0.001), number of primary dendrites (P < 0.01) and [3H]dopamine uptake (P < 0.01) of TH-IR-positive mesencephalic neurons. Similar effects were observed with 10 microm amphetamine. All neurotrophic effects were blocked by the unselective D2/D3 receptor antagonist sulpiride (5 microm) and by the selective D3 receptor antagonist SB-277011-A at a low dose (50 nm). Quinpirole and 7-OH-DPAT also increased the phosphorylation of extracellular signal-regulated kinase (ERK) within minutes, an effect blocked by pretreatment with SB-277011-A. Inhibition of the D2/D3 receptor signalling pathway to ERK was obtained with PD98059, GF109203 or LY294002, resulting in blockade of neurotrophic effects. These data suggest that dopamine agonists increase dendritic arborizations of mesencephalic dopaminergic neurons via a direct effect on D2/D3 receptors, preferentially involving D3 receptor-dependent neurotransmission.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a24662a31671029a8a975e8fa366cb8e https://pubmed.ncbi.nlm.nih.gov/18973551 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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