Studies of ATP-sensitive potassium channels on 6-hydroxydopamine and haloperidol rat models of Parkinson's disease: implications for treating Parkinson's disease?
In the present study, we first investigated the effects of unilateral 6-hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta (SNc) on the expression of subunits of ATP-sensitive potassium channels (KATP channels) in the prefrontal cortex (PFC), striatum and hippocampus of adult rats by utilizing semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry techniques. The results show that Kir6.2 and SUR2 expression in the PFC, Kir6.1, Kir6.2 and SUR1 expression in the striatum, and Kir6.1 and Kir6.2 expression in the hippocampus of injured side increased significantly after unilateral 6-OHDA lesioning of the SNc in rats. Afterward, we studied the effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KCO), on parkinsonian symptoms, which were induced by acute injection of haloperidol. The results indicate that intraperitoneal injection of Ipt (0.125 mg/kg, 0.25 mg/kg or 0.5 mg/kg) partially alleviated haloperidol-induced catalepsy and hypolocomotion. Even though the observed effects (0.5 mg/kg) are better than those of l-3,4-dihydroxyphenylalanine (L-DOPA) (100 mg/kg), Ipt (0.25 mg/kg) failed to enhance the anti-parkinsonian actions of L-DOPA (100 mg/kg). Our results suggest that KATP channels might be involved in the pathogenesis of Parkinson's disease (PD) induced in an animal model and conceptually support the idea that KATP channels may be new therapeutic targets for PD.
Wang
Sen
S
Department of Pharmacology and Neurobiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
Hu
Li-Fang
LF
Yang
Yong
Y
Ding
Jian-Hua
JH
Hu
Gang
G
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D015221:Potassium Channels / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000978:Antiparkinson Agents; D015221:Potassium Channels; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D006220:Haloperidol