title: Calcium homeostasis is dysregulated in parkinsonian patients with L-DOPA-induced dyskinesias.
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 (D1-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 [Ca2+]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/10 cells) and LID- patients (4.2 +/- 2.4 pmol/10(6) cells), with respect to controls (6 +/- 2.6 pmol/10(6) 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.
authors.affiliation: Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson's Disease, IRCCS Neurological Institute C. Mondino, Pavia, Italy. fabio.blandini@mondino.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bazzini
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Federica
authors.initials: F
authors.lastname: Saporiti
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Armentero
authors.forename: Claudio
authors.initials: C
authors.lastname: Pacchetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Zangaglia
authors.forename: Emilia
authors.initials: E
authors.lastname: Martignoni
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
mesh_terms: D000368:Aged; D017109:Akathisia, Drug-Induced / Q000209:etiology*; D000978:Antiparkinson Agents / Q000009:adverse effects*; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D007980:Levodopa / Q000009:adverse effects*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000235:genetics / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D000978:Antiparkinson Agents; D007476:Ionophores; D007783:Lactones; D008934:Mitogens; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D050637:Receptors, Dopamine D3; D012717:Sesquiterpenes; D050641:Receptors, Dopamine D5; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D007980:Levodopa; C046319:thapsigargicin; D000242:Cyclic AMP; D002118:Calcium