title: Dopaminergic modulation of apoptosis in human peripheral blood mononuclear cells: possible relevance for Parkinson's disease.
abstract: Dopamine (DA) modulates apoptosis in neuronal and non-neuronal cells, and dopaminergic pathways contribute to neurodegenerative disease. Human lymphocytes express dopaminergic receptors and DA transporters, and synthesize endogenous catecholamines, which may modulate apoptosis in these cells. In the present study, dopaminergic modulation of apoptosis was investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Twenty-four-hour DA reduced at 0.1-5 x 3 10(-6) M and enhanced at 1-5 x 310(-4) M spontaneous apoptosis. DA 1 x 310(-6) M was inhibited by the D1-like receptor antagonist SCH 23390 1 x 310(-6) M, but not by the D2-like receptor antagonists domperidone 1 x 3 10(-6) M or haloperidol 1 x 3 10(-6) M, while the effect of DA 5 x 3 10(-4) M was prevented by the antioxidants glutathione 5-10 mM or N-acetyl-l-cysteine 1-10 mM. Intracellular reactive oxygen species were respectively reduced and increased by 1-3 h incubation with DA 0.1-10 x 3 10(-6) M and 1-5x310(-4) M. Twenty-four-hour DA 1 x 3 10(-6) M or 5 x 3 10(-4) M had no effect on PBMC expression of Cu/Zn superoxide dismutase or Bcl-2; however, DA 5 x 3 10(-4) M decreased caspase-3 activity. In human PBMCs, DA seems to promote apoptosis through oxidative mechanisms but may also result in cell rescue from apoptotic death possibly through activation of D1-like receptors. The dual effect of DA on human PBMCs closely resembles that on striatal neurons. Lymphocytes of patients with Parkinson's disease may show reduced DA content and impaired DA transporter immunoreactivity. Human PBMCs may thus represent a simple and readily accessible model to study DA-related mechanisms relevant for neurodegenerative disease.
authors.affiliation: Laboratory of Pharmacology, Faculty of Medicine, University of Insubria, Varese, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Rasini
authors.forename: Maria
authors.initials: M
authors.lastname: Ossola
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.forename: Anna
authors.initials: A
authors.lastname: Mangiagalli
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrari
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bombelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Gianmario
authors.initials: G
authors.lastname: Frigo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000097:blood* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017382:Reactive Oxygen Species; D004298:Dopamine