PREFERENTIAL LOCALIZATION OF H-3 PENTOSANPOLYSULFATE TO THE URINARY-TRACT IN RATS

PREFERENTIAL LOCALIZATION OF H-3 PENTOSANPOLYSULFATE TO THE URINARY-TRACT IN RATS
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DOI:
10.1111/j.1600-0773.1987.tb01796.x
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发表时间:
1987-09-01
期刊:
PHARMACOLOGY & TOXICOLOGY
影响因子:
--
通讯作者:
TENGBLAD, A
TENGBLAD, A
中科院分区:
其他
文献类型:
--
作者:
ODLIND, B;DENCKER, L;TENGBLAD, A

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内源性糖胺聚糖可能对泌尿道具有保护作用,例如泌尿道。防止结石形成。合成硫酸化多糖戊聚糖多硫酸酯 (PPS) 已被认为可以发挥类似的保护作用,例如:通过抑制结晶和细菌抗粘附。我们研究了氚标记的 PPS 在大鼠中的分布。色谱分析显示该材料包含两个不同的峰,分子量约为 2.700 (60-70%) 和 1.000 (30-40%) 道尔顿。给Sprague-Dawley大鼠口服和静脉注射PPS(5 mg/.kg b.wt.),分别在1小时和4小时后处死大鼠,并进行全身放射自显影。静脉注射大鼠切片的放射自显影图显示,放射性在整个动物中广泛分布,结缔组织有明显的标记,而骨和软骨的放射性较低。有上肠活动,表明有一些肝脏排泄。然而,最显着的发现是尿液中的高浓度以及与尿道内壁(骨盆、输尿管和膀胱)相对应的活动的优先定位。分布相似,但口服后活性较低。在一项实验中,在麻醉下将 PPS 注入膀胱内,有或没有因滴注 0.4 M HCl 引起的上皮破坏。麻醉下膀胱内注射后,有或没有滴注 0.4 M HCl 引起的上皮破坏。用盐水剧烈冲洗后,膀胱壁中的放射性仍然被细化。在其他静脉实验中,用生理盐水剧烈冲洗,放射性仍残留在膀胱壁中。在其他静脉内实验中,膀胱被摘除、外翻并用盐水或渗透压增加的尿素冲洗。大量的放射性可用0.5M盐水冲洗掉。冲洗溶液的色谱分析显示先前在注射溶液中发现的两种 PPS 组分均存在。没有发现其他活动峰值。因此,一些注入的材料可以从膀胱壁中原封不动地回收,在膀胱壁中它似乎以中等强度进行离子结合。由于分子量 2.700 和 1.000 的 PPS 优先位于大鼠泌尿道的表面上皮,因此 PPS 在泌尿道疾病中的作用可能取决于上皮的表面涂层和/或尿液中 PPS 的浓度。
Endogenous glycosaminoglycans probably have a protective effect in the urinary tract, e.g. against stone formation. The synthetic sulphated polysaccharide pentosanopolysulphate (PPS) has been suggested to exert a similar protective effect e.g. by inhibition of crystallization and bacterial anti-adhesion. We have studied the distribution in rats of tritium-labelled PPS. Chromatography showed this material to contain two distinct peaks with approximate molecular weight around 2.700 (60-70%) and 1.000 (30-40%) daltons. PPS was administered orally and intravenously (5 mg/.kg b.wt.) to Sprague-Dawley rats, which were killed 1 and 4 hours later, respectively, and subjected to whole-body autoradiography. Autoradiograms of sections from intravenously injected rats showed an extensive distribution of radioactivity in the whole animal, with a notable labelling of connective tissues, while bone and cartilage had low activity. There was upper intestine activity, suggesting some hepatic excretion. The most conspicuous finding, however, was the high concentration in urine and a preferential localization of activity corresponding to the lining of the urinary tract (pelvis, ureter, and bladder). The distribution was similar, but the activity lower after oral administration. In one experiment, PPS was applied intravesically under anesthesia, with and without epithelial destruction caused by instillation of 0.4 M HCl. After intravescially under anaesthesia, with and without epithelial destruction caused by instillation of 0.4 M HCl. After vigorous rinsing, with saline, the radioactivity was still refined in the bladder wall. In other intravenous experiments, vigorous rinsing, with saline, the radioactivity was still remained in the bladder wall. In other intravenous experiments, the bladder was extirpated, everted and rinsed in saline or urea of increased osmolality. High amount of radioactivity could be rinsed of by 0.5M saline. Chromatography of the rinsing solution showed presence of both fractions of PPS previously found in the injection solution. No other peak of activity was found. Thus, some of the injected material could be recovered unchanged from the bladder wall, where it seems to be bound ionically with moderate strength. Since PPS of molecular weight 2.700 and 1.000 is preferentially located to the surface epithelium of the urinary tract in rats, the effects of PPS in urinary tract diseases could depend on surface coating of the epithelium and/or urinary concentrations of PPS.