Calcium homeostasis is dysregulated in parkinsonian patients with L-DOPA-induced dyskinesias.
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.
Blandini
Fabio
F
Laboratory of Functional Neurochemistry, Interdepartmental Research Center for Parkinson's Disease, IRCCS Neurological Institute C. Mondino, Pavia, Italy. fabio.blandini@mondino.it
Bazzini
Eleonora
E
Marino
Franca
F
Saporiti
Federica
F
Armentero
Marie-Therese
MT
Pacchetti
Claudio
C
Zangaglia
Roberta
R
Martignoni
Emilia
E
Lecchini
Sergio
S
Nappi
Giuseppe
G
Cosentino
Marco
M
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
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