药学学报
藥學學報
약학학보
ACTA PHARMACEUTICA SINICA
2006年
6期
565-571
,共7页
郑敏%郭莲军%徐旭林%胡还忠%宗贤刚
鄭敏%郭蓮軍%徐旭林%鬍還忠%宗賢剛
정민%곽련군%서욱림%호환충%종현강
ZD7288%超极化激活环核苷酸门控阳离子通道%场电位%氨基酸%海马
ZD7288%超極化激活環覈苷痠門控暘離子通道%場電位%氨基痠%海馬
ZD7288%초겁화격활배핵감산문공양리자통도%장전위%안기산%해마
ZD7288%hyperpolarization-activated cyclic nucleotide-gated cation channel%field potentials%amino acids%hippocampus
目的观察HCN通道特异性阻滞剂ZD7288对大鼠海马CA3区突触传递的影响.方法应用在体电生理细胞外记录技术记录大鼠海马CA3区场电位,用HPLC荧光检测技术测定海马组织氨基酸含量,观察CA3区局部微量给予ZD7288和CsCl后对低频(0.5 Hz)刺激穿通通路(perforant pathway,PP)诱发的海马CA3区群峰电位(population spike,PS)幅度及海马组织氨基酸含量的影响.结果海马CA3区分别注射ZD7288(20,100和200nmol)和CsCl(1,5和10 μmol)可引起PS幅度剂量依赖性下降;药物效应于给药后5 min开始,作用维持时间90 min以上.给予ZD7288(100nmol)大鼠海马组织谷氨酸、天冬氨酸、甘氨酸及γ-氨基丁酸含量显著降低,与生理盐水对照组比较,差异有显著性意义(P<0.01或P<0.05).结论 ZD7288可显著抑制大鼠穿通纤维-海马CA3区突触传递,并可降低海马组织氨基酸含量.
目的觀察HCN通道特異性阻滯劑ZD7288對大鼠海馬CA3區突觸傳遞的影響.方法應用在體電生理細胞外記錄技術記錄大鼠海馬CA3區場電位,用HPLC熒光檢測技術測定海馬組織氨基痠含量,觀察CA3區跼部微量給予ZD7288和CsCl後對低頻(0.5 Hz)刺激穿通通路(perforant pathway,PP)誘髮的海馬CA3區群峰電位(population spike,PS)幅度及海馬組織氨基痠含量的影響.結果海馬CA3區分彆註射ZD7288(20,100和200nmol)和CsCl(1,5和10 μmol)可引起PS幅度劑量依賴性下降;藥物效應于給藥後5 min開始,作用維持時間90 min以上.給予ZD7288(100nmol)大鼠海馬組織穀氨痠、天鼕氨痠、甘氨痠及γ-氨基丁痠含量顯著降低,與生理鹽水對照組比較,差異有顯著性意義(P<0.01或P<0.05).結論 ZD7288可顯著抑製大鼠穿通纖維-海馬CA3區突觸傳遞,併可降低海馬組織氨基痠含量.
목적관찰HCN통도특이성조체제ZD7288대대서해마CA3구돌촉전체적영향.방법응용재체전생리세포외기록기술기록대서해마CA3구장전위,용HPLC형광검측기술측정해마조직안기산함량,관찰CA3구국부미량급여ZD7288화CsCl후대저빈(0.5 Hz)자격천통통로(perforant pathway,PP)유발적해마CA3구군봉전위(population spike,PS)폭도급해마조직안기산함량적영향.결과해마CA3구분별주사ZD7288(20,100화200nmol)화CsCl(1,5화10 μmol)가인기PS폭도제량의뢰성하강;약물효응우급약후5 min개시,작용유지시간90 min이상.급여ZD7288(100nmol)대서해마조직곡안산、천동안산、감안산급γ-안기정산함량현저강저,여생리염수대조조비교,차이유현저성의의(P<0.01혹P<0.05).결론 ZD7288가현저억제대서천통섬유-해마CA3구돌촉전체,병가강저해마조직안기산함량.
Aim To study the effect of ZD7288 on synaptic transmission in the pathway from perforant pathway (PP) fibers to CA3 region in rat hippocampus. Methods The extracellular recording technique in vivo was used to record the CA3 region field potentials. High-performance liquid chromatography (HPLC) with fluorescence detection was applied to measure the content of amino acids in hippocampal tissues. The effect of ZD7288 and CsCl on the amplitudes of population spike (PS) in CA3 region evoked by stimulation (0.5 Hz) of the perforant pathway (PP) fibers, and the content of amino acids in hippocampal tissue were observed. Results Microinjection of ZD7288 (20, 100 and 200 nmol)and CsCl (1,5 and 10 μmol) into CA3 region decreased the population spike (PS) amplitudes in a dosedependent manner. The inhibitory effects appeared at 5 min after microinjection and lasted at least 90 min.In those rats treated with ZD7288 (100 nmol), the contents of glutamate, aspartate, glycine and GABA decreased significantly as compared to those of saline control ( all P<0.01, except P<0.05 for that of glycine). A similar decrease in the contents of amino acids was observed when the rats were microinjected with CsCl (5 μmol). Conclusion ZD7288 could obviously inhibit synaptic transmission in the pathway from PP fibers to CA3 region in rat hippocampus, and this action of ZD7288 may be associated with altered contents of amino acids.