Rao S B, Mehendale H M
Drug Metab Dispos. 1987 Mar-Apr;15(2):189-94.
The pulmonary uptake and accumulation of the three polyamines in intact, ventilated, and perfused rabbit lungs was investigated. Lungs were perfused using Krebs-Ringer bicarbonate buffer with albumin in which putrescine, spermidine, or spermine were included at an initial concentration of 10(-3), 10(-2), 10(-1), 5, 10, or 20 mM. At a 5 mM concentration of spermidine and spermine, the uptake by isolated lungs reached a steady state equilibrium in 20-30 min of perfusion. This did not occur for putrescine, which showed linear uptake throughout the entire period of the 60-min perfusion. The lung uptake of putrescine for all perfusate concentrations was greater than that of spermidine or spermine, but all three showed concentration-dependent linear uptake. In the presence of harmaline (1 mM) and ouabain (1 mM), isolated perfused rabbit lungs showed a decrease in uptake of putrescine although no effect was seen for spermidine and spermine. Perfusate containing decreased sodium showed no effect on putrescine uptake by isolated rabbit lungs, but there was a significant increase in the uptake of spermidine and spermine. Significant uptake of all three polyamines was also observed when incubated separately with rabbit lung slices for 60 min. HPLC analysis of lung, the perfusate samples, lung slices, and the incubation medium after a 60-min incubation did not indicate the presence of metabolites of these polyamines. Likewise, the analysis of the lung homogenate incubated with polyamines did not show any metabolites confirming the absence of detectable pulmonary metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了三种多胺在完整、通气且灌注的兔肺中的肺摄取和蓄积情况。使用含白蛋白的 Krebs-Ringer 碳酸氢盐缓冲液灌注肺,其中腐胺、亚精胺或精胺的初始浓度分别为 10(-3)、10(-2)、10(-1)、5、10 或 20 mM。在亚精胺和精胺浓度为 5 mM 时,离体肺在灌注 20 - 30 分钟后摄取达到稳态平衡。腐胺未出现这种情况,在整个 60 分钟灌注期间其摄取呈线性。所有灌注液浓度下,肺对腐胺的摄取均大于亚精胺或精胺,但三者均呈现浓度依赖性线性摄取。在存在 harmaline(1 mM)和哇巴因(1 mM)的情况下,离体灌注兔肺对腐胺的摄取减少,而亚精胺和精胺未见影响。含钠量降低的灌注液对离体兔肺摄取腐胺无影响,但亚精胺和精胺的摄取显著增加。将三种多胺分别与兔肺切片孵育 60 分钟后,也观察到了显著摄取。对孵育 60 分钟后的肺、灌注液样本、肺切片和孵育培养基进行 HPLC 分析,未表明存在这些多胺的代谢产物。同样,对与多胺孵育的肺匀浆分析也未显示任何代谢产物,证实不存在可检测到的肺代谢。(摘要截断于 250 字)