Zhai Q Z, Lai Z, Yukhananov R, Roos P, Nyberg F
Department of Pharmaceutical Bioscience, University of Uppsala, Sweden.
Neurosci Lett. 1995 Jan 23;184(2):82-5. doi: 10.1016/0304-3940(94)11174-h.
Male Sprague-Dawley rats were continuously infused with morphine through subcutaneously implanted mini-osmotic pumps over a period of 5 days. The binding of rat growth hormone (rGH) to specific sites in choroid plexus, cortex, hypothalamus, hippocampus and striatum was determined. It was found that in the acute phase of morphine administration the density of growth hormone-binding sites was significantly decreased in choroid plexus and in hypothalamus, but not in any other of the tissues studied. When tolerance to morphine was developed, the level of growth hormone-binding was restored to control level. In the acute phase, the plasma levels of GH, as measured by radioimmunoassay, correlated negatively with the density of the binding sites in choroid plexus and hypothalamus. The decrease in growth hormone-binding in these regions of the rat brain was also confirmed by SDS-polyacrylamide gel electrophoresis of cross-linked complexes of the binding entities to 125I-labelled rGH as visualized by autoradiography. In experiments, where morphine was administrated by intermittent injections, a similar decrease in rGH-binding was observed. However, the time-course of this decrease seemed to be dependent upon the route of administration. Following intracerebroventricular (i.c.v.) injections, the binding of the hormone was already affected after 30 min, whereas the binding of rGH in brain areas after subcutaneous (s.c.) injections was affected at a later stage.
将雄性斯普拉格-道利大鼠通过皮下植入的微型渗透泵持续输注吗啡，为期5天。测定大鼠生长激素（rGH）与脉络丛、皮质、下丘脑、海马体和纹状体中特定部位的结合情况。结果发现，在吗啡给药的急性期，脉络丛和下丘脑中生长激素结合位点的密度显著降低，但在其他所研究的组织中未出现这种情况。当对吗啡产生耐受性时，生长激素结合水平恢复到对照水平。在急性期，通过放射免疫测定法测得的血浆GH水平与脉络丛和下丘脑中结合位点的密度呈负相关。通过放射自显影观察到，对结合实体与125I标记的rGH的交联复合物进行SDS-聚丙烯酰胺凝胶电泳，也证实了大鼠大脑这些区域中生长激素结合的减少。在通过间歇性注射给予吗啡的实验中，观察到rGH结合出现类似减少。然而，这种减少的时间进程似乎取决于给药途径。脑室内（i.c.v.）注射后，30分钟后激素结合就已受到影响，而皮下（s.c.）注射后，大脑区域中rGH的结合在后期才受到影响。
