Britton D R, Mikusa J, Lee C H, Jarvis M F, Williams M, Kowaluk E A
Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Neurosci Lett. 1999 May 7;266(2):93-6. doi: 10.1016/s0304-3940(99)00280-3.
The effects of the systemically administered adenosine kinase (AK) inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) on the striatal adenosine (ADO) release evoked by the excitotoxin, kainic acid (KA) were examined using rat bilateral striatal microdialysis. Local KA perfusion of one rat striatum caused a significant ipsilateral elevation of striatal ADO levels compared to basal and contralateral (artificial CSF-perfused) striatal ADO levels. KA-evoked striatal ADO release was augmented in animals receiving systemic 5'd-5IT treatment (cumulative dose of 7.5 micromol/kg, i.p.) compared with i.p. vehicle controls. In contrast, 5'd-5IT administration had no significant effect on basal or contralateral (artificial CSF-perfused) striatal ADO levels. Thus, consistent with the hypothesis of 'site and event specific' potentiation of ADO by AK inhibitors, 5'd-5IT unilaterally enhanced ADO levels in the striatum where KA-induced excitotoxic injury evoked endogenous ADO release, but not at the contralateral uninjured striatum.
使用大鼠双侧纹状体微透析技术，研究了全身给药的腺苷激酶（AK）抑制剂5'-脱氧-5-碘杀结核菌素（5'd-5IT）对兴奋性毒素 kainic acid（KA）诱发的纹状体腺苷（ADO）释放的影响。与基础水平和对侧（人工脑脊液灌注）纹状体ADO水平相比，局部向一只大鼠的纹状体灌注KA导致纹状体ADO水平同侧显著升高。与腹腔注射溶媒对照相比，接受全身5'd-5IT治疗（累积剂量7.5微摩尔/千克，腹腔注射）的动物中，KA诱发的纹状体ADO释放增加。相反，5'd-5IT给药对基础或对侧（人工脑脊液灌注）纹状体ADO水平无显著影响。因此，与AK抑制剂“位点和事件特异性”增强ADO的假说一致，5'd-5IT单方面提高了KA诱导兴奋性毒性损伤诱发内源性ADO释放的纹状体中的ADO水平，但对侧未损伤的纹状体中则没有。
