Liberato José Luiz, Cunha Alexandra Olimpio Siqueira, Mortari Márcia Renata, Gelfuso Erica Aparecia, Beleboni René de Oliveira, Coutinho-Netto Joaquim, dos Santos Wagner Ferreira
Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature, University of São Paulo, Brazil.
Brain Res. 2006 Dec 8;1124(1):19-27. doi: 10.1016/j.brainres.2006.09.052. Epub 2006 Nov 13.
This study was aimed at determining the effects of FrPbAII (174 Da), a novel isolated component from Parawixia bistriata spider venom, in the CNS of Wistar rats. Considering that FrPbAII inhibits the high affinity GABAergic uptake in a dose-dependent manner, its anxiolytic and anticonvulsant effects were analyzed in well-established animal models. Injection of FrPbAII in the rat hippocampus induced a marked anxiolytic effect, increasing the occupancy in the open arms of the elevated plus maze (EC(50)=0.09 microg/microl) and increasing the time spent in the lit area of the light-dark apparatus (EC(50)=0.03 microg/microl). Anxiolytic effects were also observed considering the number of entries in the open arms of the EPM and in the lit compartment of the light-dark box. Interestingly, when microinjected bilaterally in the SNPr of freely moving rats, FrPbAII (0.6 microg/microl) effectively prevented seizures induced by the unilateral GABAergic blockade of Area tempestas (bicuculline, 0.75 microg/microl). This anticonvulsant effect was similar to that evoked by muscimol (0.1 microg/microl) and baclofen (0.6 microg/microl), but differed from that of the specific GAT1 inhibitor, nipecotic acid (0.7 microg/microl). This difference could be accounted either for the parallel action of FrPbAII over glycinergic transporters or to an inspecific activity on GABAergic transporters. Data from the present investigation might be pointing to a novel compound with interesting and yet unexplored pharmacological potential.
本研究旨在确定从双带舞蛛毒液中分离出的一种新型成分FrPbAII（174道尔顿）对Wistar大鼠中枢神经系统的影响。鉴于FrPbAII以剂量依赖性方式抑制高亲和力GABA能摄取，我们在成熟的动物模型中分析了其抗焦虑和抗惊厥作用。在大鼠海马中注射FrPbAII可诱导显著的抗焦虑作用，增加高架十字迷宫开放臂中的停留时间（半数有效浓度[EC(50)] = 0.09微克/微升），并增加明暗箱亮区的停留时间（EC(50) = 0.03微克/微升）。从进入高架十字迷宫开放臂和明暗箱亮隔的次数来看，也观察到了抗焦虑作用。有趣的是，当在自由活动大鼠的黑质网状部双侧微量注射时，FrPbAII（0.6微克/微升）有效地预防了由颞叶区域的单侧GABA能阻断（荷包牡丹碱，0.75微克/微升）诱导的癫痫发作。这种抗惊厥作用与蝇蕈醇（0.1微克/微升）和巴氯芬（0.6微克/微升）引起的作用相似，但与特异性GAT1抑制剂尼克酸（0.7微克/微升）的作用不同。这种差异可能是由于FrPbAII对甘氨酸能转运体的平行作用，或者是对GABA能转运体的非特异性活性。本研究的数据可能指向一种具有有趣但尚未探索的药理潜力的新型化合物。
