Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman.
Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman.
复制标题
大鼠鼻粘膜非那西丁的代谢激活：与鲍曼腺的剂量依赖性结合。
作者：
E. Brittebo
在雄性Sprague-Dawley大鼠体内和体外研究了抗疟药[ring-3 H]非那西丁在鼻粘膜中的代谢和结合。如全身和光镜放射自显影所示，在高剂量[3 H]非那西丁后，但在低剂量[3 H]非那西丁后，代谢物与嗅粘膜中的Bowman腺不可逆结合。在其他组织中，当剂量增加时，放射性分布未发生变化。[3 H]-对乙酰氨基酚的放射自显影显示嗅粘膜中没有优先摄取放射性。在体外将鼻中隔与[3 H]非那西丁孵育时，观察到代谢物与Bowman腺结合，表明代谢发生在原位。在大鼠中，谷胱甘肽（GSH）耗尽预处理与佛尔酮，有一个结合的Bowman腺的嗅粘膜后，也痕量剂量的[3 H]非那西丁。GSH的加入降低了与[3 H]非那西丁孵育的9000 X g鼻粘膜上清液中发生的[3 H]非那西丁代谢物的不可逆结合。在给予100-300 mg/kg非那西丁后，嗅粘膜中的非蛋白巯基（主要是GSH）水平中度降低。总的来说，这些数据表明，非那西丁代谢和随后的GSH消耗，结合优先在鲍曼的腺体。这些数据还表明，在原位代谢活化和结合的非那西丁在大鼠鼻粘膜在高剂量的非那西丁可能在由高剂量的非那西丁诱导的大鼠鼻肿瘤的发病机制中发挥作用。
The metabolism and binding of the analgetic drug [ring-3H]phenacetin in the nasal mucosa were studied in vitro and in vivo in male Sprague-Dawley rats. As shown by whole-body and light microscopic autoradiography there was an irreversible binding of metabolites to the glands of Bowman in the olfactory mucosa after high but not after low doses of [3H]phenacetin. In the other tissues, the distribution of radioactivity was not changed when the dose was increased. Autoradiography of [3H]-acetaminophen showed no preferential uptake of radioactivity in the olfactory mucosa. At incubation of nasal septa with [3H]phenacetin in vitro, a binding of metabolites to the glands of Bowman was observed indicating that the metabolism occurred in situ. In rats, glutathione (GSH) depleted by pretreatment with phorone, there was a binding to the glands of Bowman in the olfactory mucosa also after a trace dose of [3H]phenacetin. Addition of GSH decreased the irreversible binding of [3H]phenacetin metabolites that occurred in 9000 X g nasal mucosa supernatants incubated with [3H]phenacetin. There was a moderate decrease in the level of nonprotein sulfhydryl groups, mainly GSH, in the olfactory mucosa after administration of 100-300 mg/kg phenacetin. Collectively, these data suggest that phenacetin is metabolized and subsequent to GSH depletion, bound preferentially in the glands of Bowman. The data also suggest that in situ metabolic activation and binding of phenacetin in the rat nasal mucosa at high doses may play a role in the pathogenesis of the nasal tumors induced by high doses of phenacetin in the rat.
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细胞色素 P-450 同工酶（细胞色素 P-450 PB-B）和 NADPH-细胞色素 P-450 还原酶在大鼠鼻粘膜中的定位。
影响因子：
9.7
作者：
Voigt,JM;Guengerich,FP;Baron,J
通讯作者：
Baron,J
培养的大鼠鼻粘膜对烟草特异性亚硝胺的代谢。
影响因子：
11.2
作者：
Brittebo,EB;Castonguay,A;Furuya,K;Hecht,SS
通讯作者：
Hecht,SS
DOI：
10.1073/pnas.81.5.1327
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAHLIN, DC;MIWA, GT;NELSON, SD
通讯作者：
NELSON, SD
非那西丁在仓鼠和仓鼠肝微粒体中芳基化和烷基化代谢物的形成。
影响因子：
3.6
作者：
Nelson,SD;Forte,AJ;Vaishnav,Y;Mitchell,JR;Gillette,JR;Hinson,JA
通讯作者：
Hinson,JA