【摘要】 本实验观察了CCK—8对[³H]Et与大鼠脑阿片受体结合的影响.含硫CCK—8能抑制[³H]Et与高亲和位点的结合,使K_D值增大（P<0.001）,B_max减小（P<0.01）,在10 fmol/L～Lμmol/L范围内呈量效关系.但对低亲和位点的结合没有影响.无硫CCK—8仅对[³H]Et高亲和位点的K_D值有较小程度的增大（P<0.05）,不影响B_max值.CCK—8（10 nmol/L）抑制[³H]Et与阿片受体结合的作用能被CCK受体拮抗剂谷丙酰胺（1μmol/L）所阻断.结果提示,CCK—8可能通过激活CCK受体发挥对阿片受体的抑制作用。更多还原

【Abstract】 Behavior studies suggested cholecystokinin octapeptide (CCK-8)to be an endogenous antagonist to opioid analgesia.In the present study radio-ligand binding test was adopted to analyse the possible influence of CCK-8 on [3H] etorphine binding to opiate receptors in rat brain’s synaptosomal membranes (p2).Dihydroetorphine (0.032-100 nmol/L)showed a typical displacement on [3H]etorphine(0.4 nmol/L)binding with an ICJ0of 0.66 nmol/L,whereas CCK-8 (up to 1μmol/L)could only inhibit the binding of [3H]etorphine by 30%.Scatchard analysis revealed two populations of [3H]etorphine binding sites: the high affinity sites with KD of 33.7 pmol/L and Bmax of 32.6 fmol / mg protein,and low affinity sites with KD of 1.49 nmol/L and Bmax of 85.6 fmol/mg protein CCK-8 (1 pmol/L-1μmol/L)dose-de-pendently inhibited [3H] etorphine binding tothe high affinity sites by raising the KD (up to 335%,p<0.001)and lowering Bmax(-89 % at 1μmol/L,p<0.01)without significant changes in the affinity and total number of the low affinity sites.This effect of CCK-8 (10 nmol/ L)was completely blocked by proglumide,the CCK receptor antagonist,at 1μmol/L.Unsulfated CCK-8 (0.1 nmol / L~1μmol / L),however,produced only a slight increase in KD of the high affinity sites (+64.3 %,p<0.05)without affecting Bmax.The results suggest that CCK-8 is capable of suppressing the affinity and down regulating the total number of high affinity opioid binding sites via the activation of CCK receptors.更多还原