吗啡和血管紧张素Ⅱ对大鼠脑突触小体Ca^(2+)摄取的拮抗效应

ANTAGONISTIC EFFECTS OF ANGIOTENSIN Ⅱ AND MORPHINE ON SYNAPTOSOMAL CALCIUM UPTAKE

行为实验已多次证明,脑室注射血管紧张素Ⅱ(AⅡ)可以对抗吗啡的镇痛作用,但机制不明。吗啡阻止神经末梢钙摄取被认为是其镇痛的机理之一,因此本工作研究了AⅡ和吗啡对大鼠脑突触小体^(45)Ca摄取的作用及相互关系。结果表明,吗啡(10^(-8)—10^(-6)mol/L)对^(45)Ca摄取有明显的抑制作用,10^(-7)mol/L时抑制41％(P<0.001),该效应可被吗啡受体阻断剂纳洛酮(10^(-6)mol/L)完全翻转。与吗啡的作用相反,AⅡ(10^(-8)—110^(-6)mol/L)可促进突触小体对^(45)Ca的摄取,10^(-7)mol/L时增加75％(P<0.001),该效应可被AⅡ受体阻断剂Saralasin(10^(-6)mol/L)完全翻转。将不同剂量的AⅡ(10^(-8)—10^(-6)mol/L)和10^(-8)mol/L吗啡与突触小体共同孵育,则吗啡抑制^(45)Ca摄取的作用被完全翻转。以上结果表明,AⅡ促进脑突触小体Ca^(2+)摄取,对抗了吗啡抑制Ca^(2+)摄取的作用,可能是AⅡ抗吗啡镇痛的机制之一。

Behavioral observations have repeatedly shown that the analgesic effect of morphine can be antagonized by intracerebroventricular injection of angiotensin Ⅱ(AⅡ), although mechanisms underlying the action were obscure. Since a prevention of Ca^(2+) uptake into the nerve terminals was considered as one of the mechanisms for morphine analgesia, we examined the effect of A Ⅱ and morphine on the ^(45)Ca uptake by rat brain synaptosomal preparations. Morphine of 10^(-8)—10^(-6) mol/L produced a dose-related suppression on synaptosomal ^(45)Ca uptake, which was completely reversed by the opioid antagonist naloxone of 10^(-6) mol/L. A Ⅱ of 10^(-8)—10^(-6)mol/L, on the contrary, enhanced ^(45)Ca uptake. This effect was totally abolished by saralasin, a A Ⅱ antagonist, at 10^(-6) mol/L. When synaptosomal preparations were incubated in a mixture of morphine (10^(-6)mol/L) and A Ⅱ (10^(-8)—10^(-6) mol/L), the effect of morphine was almost completely reversed. The results suggest that the distinct effect of A Ⅱ may account for, at least in part, the antagonistic effect of A Ⅱ on morphine analgesia.