Wang Rui, Boules Mona, Tiner William, Richelson Elliott
Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research, and Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Brain Res. 2004 Oct 29;1025(1-2):21-8. doi: 10.1016/j.brainres.2004.07.069.
The effect of five daily intraperitoneal (i.p.) injections of NT69L on in vitro dopamine release, uptake, and [(3)H]NT binding in rat striatal tissue was investigated. NT69L perfusion increased K(+)-evoked and electrically evoked [(3)H]DA release. NT receptor-1 antagonist SR48692 inhibited the stimulatory effect of NT69L on K+-evoked [(3)H]DA release, but not on electrical depolarization. Pretreatment with NT69L, in vivo, daily for 5 days, did not cause significant change in K(+) evoked [(3)H]DA release, but reduced electrically evoked [(3)H]DA release induced by NT69L perfusion. Repeated perfusion with NT69L in vitro caused marked reduction on K(+)-evoked [(3)H]DA release and no change in electrically evoked [(3)H]DA release. [(3)H]NT binding was not significantly changed by one injection but was decreased after five injections of NT69L. Desensitization to the effects of NT69L in vitro was different depending upon whether tissue was preexposed to the compound in vivo or in vitro. These results provide further proof for the involvement of different NT receptor subtypes in mediating the effect of NT69L on dopamine release evoked by K(+) or electrical depolarization.
研究了连续5天腹腔注射NT69L对大鼠纹状体组织体外多巴胺释放、摄取及[³H]NT结合的影响。NT69L灌注增加了K⁺诱发和电刺激诱发的[³H]多巴胺释放。NT受体-1拮抗剂SR48692抑制了NT69L对K⁺诱发的[³H]多巴胺释放的刺激作用，但对电去极化无抑制作用。体内连续5天每天用NT69L预处理，并未使K⁺诱发的[³H]多巴胺释放发生显著变化，但降低了NT69L灌注诱导的电刺激诱发的[³H]多巴胺释放。体外重复用NT69L灌注导致K⁺诱发的[³H]多巴胺释放显著减少，而电刺激诱发的[³H]多巴胺释放无变化。单次注射NT69L对[³H]NT结合无显著影响，但5次注射后[³H]NT结合减少。体外对NT69L作用的脱敏作用因组织是在体内还是体外预先暴露于该化合物而有所不同。这些结果进一步证明了不同的NT受体亚型参与介导NT69L对K⁺或电去极化诱发的多巴胺释放的作用。
