强啡肽A和CCK—8对大鼠脊髓突触小体摄取^45Ca的影响

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。

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

Cholecystokinin octapeptide (CCK-8) and angiotensin I (AI) have been shown in behavioral studies being endogenous antiopioid substrates (AOS). To assess their antiopioid mechanism at postreceptor level, we observed the effects of the three opioids and the two AOS on 45Ca uptake of the rat spinal synaptosomal preparations. Morphine, Dyn A and DPDPE at concentrations of 10 nmol/L to 1 mumol/L, produced a mild suppression of 45Ca uptake of synaptosomal preparations from ventral spinal cord. CCK-8 showed a mild suppression only at a concentration of 1 mumol/L. In synaptosomes prepared from dorsal spinal cord, Dyn A but not morphine or DPDPE, produced a strong inhibition of 45Ca uptake which was blocked by nor-BNI, a kappa receptor antagonist, at 1 mumol/L. While CCK-8 (10 nmol/L to 1 mumol/L) also suppressed 45Ca uptake, it could antagonize the suppressive effect induced by Dyn A. In contrast to CCK-8, AI (10 nmol/L to 1 mumol/L) influenced neither on synaptosomal 45Ca uptake, nor on Dyn A suppression of 45Ca uptake. The results presented above fit very well with our behavioral studies, i.e., CCK-8 antagonized opioid analgesia in both the brain and the spinal cord, whereas AI antagonized opioid analgesia in the brain but not in the spinal cord. It is therefore concluded that antagonism of the opioid suppression of synaptosomal 45Ca uptake might be one of the mechanisms for the antiopioid activity of CCK-8 and AI.