Calcium homeostasis is dysregulated in Parkinsonian patients with L-DOPA-induced dyskinesias

Fabio Blandini, Eleonora Bazzini, Franca Marino, Federica Saporiti, Marie Therese Armentero, Claudio Pacchetti, Roberta Zangaglia, Emilia Martignoni, Sergio Lecchini, Giuseppe Nappi, Marco Cosentino

Research output: Contribution to journalArticlepeer-review

Abstract

Long-term treatment of Parkinson disease (PD) is frequently associated with l-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LIDs). L-DOPA-induced dyskinesias are likely due to changes in the signal transduction pathways, at the striatal level, related to pulsatile stimulation of dopamine receptors. We investigated whether markers of this phenomenon can also be detected peripherally. We analyzed mRNA expression for D5 (D 1-like) and D3 (D2-like) receptors and levels of second messengers, such as cAMP and free intracellular Ca2+ ([Ca2+]i), in peripheral blood lymphocytes of PD patients with (LID+) or without LIDs (LID-). Patients with PD showed depressed [Ca 2+]i rise in response to mitogen-induced activation. The defect was more pronounced in LID+ (-33% with respect to healthy controls) than in LID- patients (-20%). Peripheral blood lymphocyte levels of cAMP were decreased in both LID+ (3.8 ± 2.9 pmol/106 cells) and LID- patients (4.2 ± 2.4 pmol/106 cells), with respect to controls (6 ± 2.6 pmol/106 cells). No differences were found in dopamine receptor mRNA expression. Our results demonstrate that second messenger levels are altered in the peripheral blood lymphocytes of PD patients treated with dopaminergic agents and that patients with LIDs show further alterations in the regulation of [Ca2+]i homeostasis. This may represent a distinctive trait of patients prone to develop dyskinetic movements.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalClinical Neuropharmacology
Volume32
Issue number3
DOIs
Publication statusPublished - May 2009

Keywords

  • Dopamine receptors
  • Lymphocytes
  • Parkinson disease
  • Second messengers
  • Therapy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pharmacology (medical)
  • Pharmacology

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