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

Yan Ling Yang, Chang Hong Meng, Jian Hua Ding, Hai Rong He, Kevin Ellsworth, Jie Wu, Gang Hu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits KATP 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 KATP 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 KATP 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 KATP channels. Collectively, Ipt may serve as a novel and effective drug for PD therapy.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalBrain Research
Volume1049
Issue number1
DOIs
StatePublished - Jul 5 2005
Externally publishedYes

Keywords

  • ATP-sensitive potassium channel
  • Glutamate transporter
  • Glutamate uptake
  • Iptakalim hydrochloride
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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