Killian A K, Schuster C R, Wainer B H
J Pharmacol Exp Ther. 1981 Jun;217(3):820-7.
Antimorphine globulin was used to study the mechanism by which naloxone produces a contracture in ileal strips removed from morphine pellet-implanted guinea pigs. Although the antibodies effectively reversed the depressant actions of morphine on electrically stimulated contractions in both naive and tolerant tissues, neither monkey antimorphine (Kd = 1.43 x 10(-7)M) nor goat antimorphine (Kd = 1.36 x 10(-9)M) were able to elicit a naloxone-like contracture. The rate of attenuation of tissue sensitivity to naloxone was measured and no changes were observed after incubation in the presence of monkey antimorphine globulin. High-affinity goat antimorphine globulin, however, was able to accelerate the rate of attenuation of tissue sensitivity to naloxone. The naloxone contracture was accompanied by release of material reactive with morphine antiserum in a radioimmunoassay. The quantities of material were in excess of what could be bound by opiate receptors present in the tissue. Possible mechanisms of naloxone sensitivity observed in the isolated ileum are discussed.
使用抗吗啡球蛋白来研究纳洛酮在从植入吗啡丸剂的豚鼠身上取下的回肠条中产生挛缩的机制。尽管这些抗体有效地逆转了吗啡对未接触过吗啡和产生耐受性的组织中电刺激收缩的抑制作用,但猴抗吗啡(解离常数Kd = 1.43×10⁻⁷M)和山羊抗吗啡(Kd = 1.36×10⁻⁹M)均无法引发类似纳洛酮的挛缩。测量了组织对纳洛酮敏感性的衰减速率,在猴抗吗啡球蛋白存在下孵育后未观察到变化。然而,高亲和力的山羊抗吗啡球蛋白能够加速组织对纳洛酮敏感性的衰减速率。纳洛酮挛缩伴随着在放射免疫测定中与吗啡抗血清发生反应的物质的释放。这些物质的量超过了组织中存在的阿片受体所能结合的量。讨论了在离体回肠中观察到的纳洛酮敏感性的可能机制。