强啡肽A和CCK-8对大鼠脊髓突触小体摄取^(45)Ca的影响

EFFECTS OF DYNORPHIN A AND CCK-8 ON SYNAPTOSOMAL ^(45)Ca UPTAKE OF THE RAT SPINAL CORD

为了探讨血管紧张素Ⅱ(AⅡ)和八肽胆囊收缩素(CCK-8)这两种肽的抗阿片作用机理,本实验中观察了三种阿片类物质(吗啡、强啡肽和 DPDPE)和两种抗阿片物质(AⅡ和 CCK-8)对大鼠脊髓突触小体摄取^(45) Ca 的影响。结果表明:(1)在脊髓腹柱突触小体上,10nmol/L—1μmol/L 的吗啡、强啡肽 A(Dyn A)和 DPDPE 对^(45)Ca 摄取均有较弱的抑制作用;(2)CCK-8在浓度高达lμmol/L 时对^(45)Ca 摄取有较弱的抑制作用;(3)AⅡ在浓度高达lμmol/L时也不影响腹柱突触小体摄取^(45)Ca;(4)在背柱的突触小体制备中,上述阿片物质中 Dyn A 对^(45)Ca 摄取有较强的抑制作用,并被 k 受体阻断剂 nor-BNI 所阻断。10和100nmol/L 的 CCK-8能翻转lμmol/L Dyn A 对^(45)Ca 摄取的抑制作用;(5)A Ⅱ不能翻转Dyn A 的抑制作用。以上结果提示,CCK-8阻断 Dyn A 抑制脊髓背柱突触小体摄取 Ca^(2+)的作用可能是其行为学中抗阿片作用的机理之一。AⅡ对脊髓 Ca^(2+)摄取和 Dyn A 抑制脊髓 Ca^(2+)摄取的作用皆无影响,与行为学中观察到的 AⅡ在脊髓内不能对抗阿片镇痛的现象一致,进一步说明 CCK-8和AⅡ拮抗阿片类物质对神经末梢 Ca^(2+)摄取的影响可能是其抗阿片作用的重要机理之一。

Cholecystokinin octapeptide(CCK-8)and angiotensin Ⅱ(AⅡ)have been shownin behavioral studies being endogenous antiopioid substrates(AOS).To assess theirantiopioid mechanism at postreceptor level,we observed the effects of the threeopioids and the two AOS on ^(45)Ca uptake of the rat spinal synaptosomal prepara-tions.Morphine,Dyn A and DPDPE at concentrations of 10 nmol/L to 1 μmol/L,produced a mild suppression of ^(45)Ca uptake of synaptosomal preparations fromventral spinal cord.CCK-8 showed a mild suppression only at a concentration of1 μmol/L.In synaptosomes prepared from dorsal spinal cord,Dyn A but notmorphine or DPDPE,produced a strong inhibition of ^(45)Ca uptake which was blockedby nor-BNI,a κ receptor antagonist,at 1 μmol/L.While CCK-8(10 nmol/L to1 μmol/L)also suppressed ^(45)Ca uptake,it could antagonize the suppressiveeffect induced by Dyn A.In contrast to CCK-8,AⅡ(10 nmol/L to 1 μmol/L)influenced neither on synaptosomal ^(45)Ca uptake,nor on Dyn A suppression of^(45)Ca uptake.The results presented above fit very well with our behavioral studies,i.e.,CCK-8antagonized opioid analgesia in both the brain and the spinal cord,whereas AⅡantagonized opioid analgesia in the brain but not in the spinal cord.It is there-fore concluded that antagonism of the opioid suppression of synaptosomal ^(45)Cauptake might be one of the mechanisms for the antiopioid activity of CCK-8 andAⅡ.