Hershman K M, Taylor D A, Fleming W W
Department of Pharmacology and Toxicology, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown 26506-9223, USA.
Mol Pharmacol. 1995 Apr;47(4):726-9.
Adaptive supersensitivity in the guinea pig vas deferens has been shown previously to be associated with decreases in transmembrane potential, Na+/K+-ATPase activity, [3H]ouabain binding sites, and density of the alpha 2 subunit of the pump. One of several procedures that induce adaptive supersensitivity in the guinea pig vas deferens is neurotransmitter depletion by chronic administration of reserpine. Guinea pigs were treated with reserpine (1.0 mg/kg/day, intraperitoneally) for 2, 5, or 8 days. Tissues were homogenized and the concentration of the alpha 2 subunit was quantified by use of the selective antibody McB2, slot blot analysis, enhanced chemiluminescence, and densitometric analysis. As reported previously, the concentration of the alpha 2 protein was reduced 41% after 5 days of pretreatment. The reduction was maintained at 8 days (37%). However, there was no change from control after 2 days of pretreatment with reserpine. Thus, the time course of the decline in the alpha 2 subunit is similar to that of the appearance of supersensitivity, depolarization, and the declines in Na+/K+-ATPase and [3H]ouabain binding established earlier. Based upon results in the literature for several different tissues and species, membrane depolarization and decreases in Na+/K+ pump sites may represent widely occurring adaptive mechanisms.
先前已表明,豚鼠输精管中的适应性超敏反应与跨膜电位降低、钠钾ATP酶活性降低、[3H]哇巴因结合位点减少以及该泵α2亚基密度降低有关。在豚鼠输精管中诱导适应性超敏反应的几种方法之一是通过长期给予利血平使神经递质耗竭。将豚鼠用利血平(1.0毫克/千克/天,腹腔注射)处理2、5或8天。将组织匀浆,并使用选择性抗体McB2、狭缝印迹分析、增强化学发光和光密度分析对α2亚基的浓度进行定量。如先前报道,预处理5天后,α2蛋白浓度降低了41%。在8天时降低维持在37%。然而,利血平预处理2天后与对照相比没有变化。因此,α2亚基下降的时间进程与超敏反应的出现、去极化以及先前确定的钠钾ATP酶和[3H]哇巴因结合的下降相似。基于针对几种不同组织和物种的文献结果,膜去极化和钠钾泵位点的减少可能代表广泛存在的适应性机制。