Involvement of calcium in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced experimental parkinsonism
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Involvement of calcium in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP)-induced experimental
parkinsonism
|
|
| Creator |
Samantaray, S
Mohanakumar, K P |
|
| Subject |
Cell Biology & Physiology
|
|
| Description |
Parkinson’s disease, a progressive neurodegenerative disorder, involves the
selective degeneration of A9 substantia nigra neurons in the brain. In the
present study, we hypothesize that the active form of the parkinsonian toxin,
1-methyl-4-phenyl pyridinium ion (MPP+) acts as a Ca2+ channel blocker.
The study explores the Ca2+-involvement in this selective neurodegeneration
at three levels: (i) subcellular level aiming to assess the intrasynaptosomal
Ca2+ flux using Fura-2AM; (ii) tissue level employing HPLC-electrochemistry
to monitor dopamine release from striatal slices; and (iii) organism level
involving in vivo studies by pharmacologically intervening with L-type
dihydropyridine Ca2+ channel agonist, (±)-Bay K8644 and antagonist,
nicardipine. The active metabolite, MPP+ was used for in vitro and ex vivo
experiments whereas for in vivo investigations, Balb/c mice were injected
with MPTP. In vivo effects of calcium channel agonist, Bay K8644 and
antagonist, nicardipine with and without MPTP were monitored for different
parameters such as monoamine oxidase-B activity, tyrosine hydroxylation,
MPP+ formation in the striatum, levels of reduced (GSH) and oxidized
glutathione (GSSG), and striatal DA employing HPLC-electrochemistry. In
the present study we observed MPP+ causes an increase in intrasynaptosomal
Ca2+, culminating in DA release from the striatum, which is sensitive to Ltype
dihydropyridine Ca2+, channel modulation. Our studies with (±)-Bay
K8644 and nicardipine affirmed the involvement of L-type Ca2+ channels in
MPTP-neurotoxicity. Relevant findings from the study proved our hypothesis:
MPP+ being a Ca2+ channel blocker, acting at the L-type Ca2+ channels.
Keywords: Parkinson’s disease, methylphenyl tetrahydropyridine, calcium,
calcium channel, neurodegeneration.
|
|
| Date |
2003
|
|
| Type |
Conference or Workshop Item
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/1075/1/3_4_JN_2003.pdf
Samantaray, S and Mohanakumar, K P (2003) Involvement of calcium in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced experimental parkinsonism. In: Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neurochemistry, WANCHAI, PEOPLES R CHINA. |
|
| Relation |
http://onlinelibrary.wiley.com/doi/10.1046/j.1474-1644.2003.2175_9.x/pdf
http://www.eprints.iicb.res.in/1075/ |
|