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Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats.
J Neurosci Res. 2005 May 01; 80(3):442-9.JN

Abstract

Our previous studies revealed that iptakalim, a novel ATP-sensitive potassium channel opener, has a significant neuroprotective function against ischemia in vivo or rotenone-induced neurotoxicity in vitro. To investigate the potential pharmaceutical benefit of ATP-sensitive potassium channel openers on neurodegenerative diseases, we studied the effects of iptakalim and diazoxide, a selective mitochondrial ATP-sensitive potassium channel opener, on the rotenone-induced nigrostriatal degeneration in rats. Iptakalim (1.5 mg/kg/day, orally) or diazoxide (1.5 mg/kg/day, orally) alone was administered to rats for 3 days, and then for 4 weeks was used daily with an injection of rotenone (2.5 mg/kg/day, subcutaneously) 1 hr later each time. The results showed that rotenone-infused rats exhibited parkinsonian symptoms and had dopamine depletion in the striatum and substantia nigra. Pretreatment with iptakalim or diazoxide prevented rotenone-induced catalepsy and the reduction of striatum dopamine contents. Moreover, iptakalim and diazoxide reduced the enzymatic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. These neuroprotective effects of iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. In conclusion, our data suggested that mitochondrial ATP-sensitive potassium channels might play a key role in preventing both parkinsonian symptoms and neurochemistry alterations induced by rotenone in rats. The selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for prevention and treatment of neurodegenerative disorders such as Parkinson's disease.

Authors+Show Affiliations

Yang Y
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Liu X
No affiliation info available
Long Y
No affiliation info available
Wang F
No affiliation info available
Ding JH
No affiliation info available
Liu SY
No affiliation info available
Sun YH
No affiliation info available
Yao HH
No affiliation info available
Wang H
No affiliation info available
Wu J
No affiliation info available
Hu G
No affiliation info available

MeSH

ATP-Binding Cassette TransportersAdenosine TriphosphateAnimalsBasal GangliaBrainBrain ChemistryCatalepsyDiazoxideDisease Models, AnimalDopamineDown-RegulationDrug Administration ScheduleMaleNerve Tissue ProteinsNeuroprotective AgentsNitric Oxide SynthaseNitric Oxide Synthase Type IParkinsonian DisordersPotassium Channel BlockersPotassium Channels, Inwardly RectifyingPropylaminesRNA, MessengerRatsRats, Sprague-DawleyRotenoneUncoupling Agents

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15795934

Citation

Yang, Yong, et al. "Systematic Administration of Iptakalim, an ATP-sensitive Potassium Channel Opener, Prevents Rotenone-induced Motor and Neurochemical Alterations in Rats." Journal of Neuroscience Research, vol. 80, no. 3, 2005, pp. 442-9.
Yang Y, Liu X, Long Y, et al. Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats. J Neurosci Res. 2005;80(3):442-9.
Yang, Y., Liu, X., Long, Y., Wang, F., Ding, J. H., Liu, S. Y., Sun, Y. H., Yao, H. H., Wang, H., Wu, J., & Hu, G. (2005). Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats. Journal of Neuroscience Research, 80(3), 442-9.
Yang Y, et al. Systematic Administration of Iptakalim, an ATP-sensitive Potassium Channel Opener, Prevents Rotenone-induced Motor and Neurochemical Alterations in Rats. J Neurosci Res. 2005 May 1;80(3):442-9. PubMed PMID: 15795934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systematic administration of iptakalim, an ATP-sensitive potassium channel opener, prevents rotenone-induced motor and neurochemical alterations in rats. AU - Yang,Yong, AU - Liu,Xing, AU - Long,Yan, AU - Wang,Fang, AU - Ding,Jian-Hua, AU - Liu,Su-Yi, AU - Sun,Ye-Hong, AU - Yao,Hong-Hong, AU - Wang,Hai, AU - Wu,Jie, AU - Hu,Gang, PY - 2005/3/30/pubmed PY - 2005/7/27/medline PY - 2005/3/30/entrez SP - 442 EP - 9 JF - Journal of neuroscience research JO - J Neurosci Res VL - 80 IS - 3 N2 - Our previous studies revealed that iptakalim, a novel ATP-sensitive potassium channel opener, has a significant neuroprotective function against ischemia in vivo or rotenone-induced neurotoxicity in vitro. To investigate the potential pharmaceutical benefit of ATP-sensitive potassium channel openers on neurodegenerative diseases, we studied the effects of iptakalim and diazoxide, a selective mitochondrial ATP-sensitive potassium channel opener, on the rotenone-induced nigrostriatal degeneration in rats. Iptakalim (1.5 mg/kg/day, orally) or diazoxide (1.5 mg/kg/day, orally) alone was administered to rats for 3 days, and then for 4 weeks was used daily with an injection of rotenone (2.5 mg/kg/day, subcutaneously) 1 hr later each time. The results showed that rotenone-infused rats exhibited parkinsonian symptoms and had dopamine depletion in the striatum and substantia nigra. Pretreatment with iptakalim or diazoxide prevented rotenone-induced catalepsy and the reduction of striatum dopamine contents. Moreover, iptakalim and diazoxide reduced the enzymatic activities and mRNA levels of inducible nitric oxide synthase elicited by chronic administration of rotenone. These neuroprotective effects of iptakalim and diazoxide were abolished by 5-hydroxydecanoate, a selective mitochondrial ATP-sensitive potassium channel blocker. In conclusion, our data suggested that mitochondrial ATP-sensitive potassium channels might play a key role in preventing both parkinsonian symptoms and neurochemistry alterations induced by rotenone in rats. The selective activation of mitochondrial ATP-sensitive potassium channels may provide a new therapeutic strategy for prevention and treatment of neurodegenerative disorders such as Parkinson's disease. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15795934/Systematic_administration_of_iptakalim_an_ATP_sensitive_potassium_channel_opener_prevents_rotenone_induced_motor_and_neurochemical_alterations_in_rats_ DB - PRIME DP - Unbound Medicine ER -