PUTRESCINE AND 5-HYDROXYTRYPTAMINE ACCUMULATION IN RAT LUNG SLICES - CELLULAR-LOCALIZATION AND RESPONSES TO CELL-SPECIFIC LUNG INJURY

PUTRESCINE AND 5-HYDROXYTRYPTAMINE ACCUMULATION IN RAT LUNG SLICES - CELLULAR-LOCALIZATION AND RESPONSES TO CELL-SPECIFIC LUNG INJURY
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DOI:
10.1016/0041-008x(87)90198-0
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发表时间:
1987-10-01
影响因子:
3.8
通讯作者:
ALDRIDGE, WN
ALDRIDGE, WN
中科院分区:
医学3区
文献类型:
--
作者:
NEMERY, B;SMITH, LL;ALDRIDGE, WN

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在氚标记的腐胺(2.5μM)或5HT(0.5μM)累积到大鼠肺切片中后,通过光学显微镜水平的放射自显影确定腐胺(1,4-二氨基丁烷)和5-羟色胺(5HT)的细胞定位。腐胺标记被发现存在于 II 型肺泡上皮细胞和细支气管非纤毛 (Clara) 细胞中,也可能存在于 I 型肺泡上皮细胞中。 5HT标记的模​​式与腐胺的标记模式明显不同,因为实质上被广泛标记,在II型细胞中没有优先位置,但对大血管内皮和胸膜间皮有强烈标记。在正常大鼠和用 O,S,S-三甲基二硫代磷酸酯(OSSMe,11 至 95 mg/kg,口服)和百草枯预处理的大鼠的肺切片中,研究了组织摄取 [3H]腐胺(2.5 至 80 μM)和 [14C]5HT(0.5 至 16 μM;两者以 5 比 1 的摩尔比同时存在)的表观动力学参数。 (20mg/kg,腹膜内),或与α-萘基硫脲(ANTU,5或10mg/kg,腹膜内)一起。 OSSMe和百草枯用作肺上皮损伤剂的模型,ANTU用作肺内皮损伤剂的模型。使用 OSSMe 和百草枯处理后,5HT 摄取的 Vmax 显着增加(Km 没有变化)。 ANTU 治疗后,5HT 摄取的 Vmax 没有变化(5 mg/kg)或增加(10 mg/kg,Km 也增加)。这些结果表明,在肺切片中,对肺损伤的反应可能与 5HT 积累的增加有关。用 OSSMe 和百草枯处理后,腐胺吸收的 Vmax 显着降低(Km 没有变化)。 ANTU 处理后,腐胺摄取的 Vmax 没有变化(5 mg/kg)或降低(10 mg/kg,Km 无变化)。这些结果表明腐胺摄取减少是肺上皮损伤的敏感指标。
The cellular localization of putrescine (1,4-diaminobutane) and 5-hydroxytryptamine (5HT) following the accumulation of tritium-labeled putrescine (2.5 .mu.M) or 5HT (0.5 .mu.M) into rat lung slices was determined by autoradiography at the light microscope level. Putrescine labeling was found to occur in type II alveolar epithelial cells and in bronchiolar nonciliated (Clara) cells, and possibly also in type I alveolar epithelial cells. The pattern of 5HT labeling was clearly different from that with putrescine, since the parenchyma was diffusely labeled with no preferential location in type II cells, but with strong labeling of the endothelium of large vessels and also the pleural mesothelium. The apparent kinetic parameters for the tissue uptake of [3H]putrescine (2.5 to 80 .mu.M) and [14C]5HT (0.5 to 16 .mu.M; both being simultaneously present in a 5 to 1 molar ratio) were studied in lung slices from normal rats and rats pretreated with O,S,S-trimethyl phosphorodithioate (OSSMe, 11 to 95 mg/kg, po), with paraquat (20 mg/kg, ip), or with .alpha.-naphthylthiourea (ANTU, 5 or 10 mg/kg, ip). OSSMe and paraquat were used as models or pulmonary epithelium-damaging agents, and ANTU was taken as a model for a pulmonary endothelium-damaging agent. The Vmax for the uptake of 5HT was significantly increased (without change in Km) following treatment with OSSMe and paraquat. Following ANTU treatment the Vmax for the uptake of 5HT was unchanged (5 mg/kg) or increased (10 mg/kg, Km also increased). These results indicate that in lung slices the response to lung injury may be associated with an increased accumulation of 5HT. The Vmax for the uptake of putrescine was significantly decreased (without change in Km) following treatment with OSSMe and paraquat. Following ANTU treatment the Vmax for the uptake of putrescine was unchanged (5 mg/kg) or decreased (10 mg/kg, no change in Km). These results suggest that a decreased putrescine uptake is a sensitive index of pulmonary epithelial damage.