Welch S P, Olson K G
Department of Pharmacology & Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613.
Life Sci. 1991;48(19):1853-61. doi: 10.1016/0024-3205(91)90241-3.
Synaptosomes were prepared from morphine-tolerant and non-tolerant mice. Significantly higher levels of basal free intracellular calcium were observed in the synaptosomes from the opiate-tolerant mice compared to synaptosomes from non-tolerant mice (468 nM versus 328 nM, respectively). In addition, morphine (1 microM) failed to attenuate KCl-induced rises in intracellular calcium in the synaptosomes from the tolerant mice. Conversely, morphine produced a concentration-related, naloxone-reversible attenuation of 50 mM KCl-induced rises in intracellular calcium in the synaptosomes from the non-tolerant mice. Omega conotoxin, which blocks both "L" and "N" type calcium channels, attenuated KCl-stimulated rises in intracellular calcium only in synaptosomes from non-tolerant mice. BAY-K 8644, an "L-type" calcium channel agonist, produced nifedipine-reversible increases in intracellular calcium in the synaptosomes from the tolerant animals only. These data suggest that chronic exposure to morphine results in an alteration in either the number of the activation state of calcium channels in the membrane. Changes in intracellular free calcium may be the final common pathway through which neurons adapt to the chronic exposure to morphine.
从吗啡耐受和非耐受小鼠制备突触体。与非耐受小鼠的突触体相比，在阿片类耐受小鼠的突触体中观察到基础游离细胞内钙水平显著更高（分别为468 nM和328 nM）。此外，吗啡（1 μM）未能减弱耐受小鼠突触体中氯化钾诱导的细胞内钙升高。相反，吗啡对非耐受小鼠突触体中50 mM氯化钾诱导的细胞内钙升高产生浓度相关的、纳洛酮可逆的减弱作用。ω-芋螺毒素可阻断“L”型和“N”型钙通道，仅在非耐受小鼠的突触体中减弱氯化钾刺激的细胞内钙升高。BAY-K 8644是一种“L型”钙通道激动剂，仅在耐受动物的突触体中产生硝苯地平可逆的细胞内钙增加。这些数据表明，长期接触吗啡会导致膜中钙通道的数量或激活状态发生改变。细胞内游离钙的变化可能是神经元适应长期接触吗啡的最终共同途径。
