Iptakalim hydrochloride protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models

Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits K ATP channel activation. Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. Chronic exposure of cultured PC12 cells to neurotoxins, suc...

Full description

Saved in:
Bibliographic Details
Published in:Brain research 2005-07, Vol.1049 (1), p.80-88
Main Authors: Yang, Yan-Ling, Meng, Chang-Hong, Ding, Jian-Hua, He, Hai-Rong, Ellsworth, Kevin, Wu, Jie, Hu, Gang
Format: Article
Language:English
Subjects:
Amino Acid Transport System X-AG - drug effects
Amino Acid Transport System X-AG - metabolism
Animals
Anticonvulsants. Antiepileptics. Antiparkinson agents
ATP-sensitive potassium channel
Biological and medical sciences
Cerebral Cortex - drug effects
Cerebral Cortex - metabolism
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Glutamate transporter
Glutamate uptake
Glutamic Acid - drug effects
Glutamic Acid - metabolism
Iptakalim hydrochloride
Male
Medical sciences
Neostriatum - drug effects
Neostriatum - metabolism
Nervous system (semeiology, syndromes)
Nervous system as a whole
Neurology
Neuropharmacology
Neuroprotection
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Neurotoxins - pharmacology
Parkinson's disease
Parkinsonian Disorders - drug therapy
PC12 Cells
Pharmacology. Drug treatments
Potassium Channels - drug effects
Potassium Channels - metabolism
Propylamines - pharmacology
Propylamines - therapeutic use
Rats
Rats, Sprague-Dawley
Synaptosomes - drug effects
Synaptosomes - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits K ATP channel activation. Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. Chronic exposure of cultured PC12 cells to neurotoxins, such as 6-OHDA, MPP +, or rotenone, decreased overall [ 3H]-glutamate uptake in a concentration-dependent manner. Pre-treatment using 10 μM Ipt significantly protected cells against neurotoxin-induced glutamate uptake diminishment, and this protection was abolished by the K ATP channel blocker glibenclamide (20 μM), suggesting that the protective mechanisms may involve the opening of K ATP channels. In 6-OHDA-treated rats (as an in vivo Parkinson's disease model), [ 3H]-glutamate uptake was significantly lower in synaptosomes isolated from the striatum and cerebral cortex, but not the hippocampus. Pre-conditioning using 10, 50, and 100 μM Ipt significantly restored glutamate uptake impairment and these protections were abolished by blockade of K ATP channels. It is concluded that Ipt exhibits substantial protection of cells against neurotoxicity in in vitro and in vivo models. The cellular mechanisms of this protective effect may involve the opening of K ATP channels. Collectively, Ipt may serve as a novel and effective drug for PD therapy.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2005.04.073