八肽胆囊收缩素对抗吗啡抑制大鼠脑突触小体钙摄取的作用

用大鼠脑的膜制备观察吗啡和CCK-8对突触小体摄取~(45)Ca~(2+)的影响。吗啡(10 nmol/L～1μmo1/L)抑制突触小体对~(45)Ca的摄取,该作用能被1μmol/L纳洛酮完全阻断。CCK-8(10nmol/L～1μmol/L)本身能抑制突触小体~(45)Ca摄取,但它在10nmol/L和100 nmol/L时能对抗吗啡对~(45)Ca摄取的抑制作用,浓度提高到1μmol则不能对抗吗啡的这一作用。CCK-8抑制突触小体摄取~(45)Ca,以及对抗吗啡的~(45)Ca摄取抑制的作用,皆能被CCK受体拮抗剂丙谷酰胺(2μmol/L)所阻断.捉示CCK-8是通过激动CCK受体而拮抗吗啡抑制~(45)Ca摄取的,CCK-8的这一拮抗作用可能是其抗阿片作用的机理之一.

Antagonism of the suppressive effect of morphine on rat brain synaptosomal ~(45)Ca uptake by cholecystokinin octapeptide

Previous observations implied that cholccystokinin oclapcptidc(CCK-8)was a strong endogenous anti-opioid substrate,though the mechanisms of aetion were obscure.Since the prevention of 45Ca2+ uptakc into the nerve terminals was considered as one of the mechanisms for morphine analgesia,we sought to examine whether CCK-8 had an augmentative effect on 45Ca uptake or was a blockade on the effect of morphine on 45Ca uptake by way of rat brain synaptosomal preparations(P2).The resultindicated that morphine at concentrations of 0.01-1μmol/L produced a suppression on synaptosomal 45Ca uptake(-41%,at 0.1 μmol/L,p<0.001).This supprcssivc effect was completely blocked by the opioid antagonist naloxonc at 1/imol/L.CCK-8(0.01-1 μmol/L)also induced a decrease in 45Ca uptake(-10-40%,p<0.01),which was completely blocked by CCK receptor antagonist proglumidc at 1μmol/L.However,CCK-8 at 0.01 and 0.1μmol/L could antagonize the suppressivc effect of morphinc(1μmol/L)on 45Ca uptake,and this antagonistic effect could also be blocked by proglumide(1μmol/L).At higher concentrations(1 and 10 μmol/L),CCK-8 failed to antagonize the effect of morphine.The results suggest that at low concentrations CCK-8 could antagonize the suppressivc effect of morphine on 45Cauptake via the activation of CCK receptor,and this effect may constitute one of the mechanisms for the anti-opioid activity of CCK-8