Humphreys M H, Etheredge S B, Lin S Y, Ribstein J, Marton L J
Division of Nephrology, San Francisco General Hospital 94110.
Am J Physiol. 1988 Aug;255(2 Pt 2):F270-7. doi: 10.1152/ajprenal.1988.255.2.F270.
We determined the role of ornithine decarboxylase (ODC) in compensatory renal hypertrophy (CRH) by relating renal ODC activity and polyamine content to kidney size, expressed as a percent of body weight, 1 wk after unilateral nephrectomy (UN). In normal rats, renal ODC activity increased from 11.0 +/- 7.4 (SD) to 36.7 +/- 15.4 pmol 14CO2.min-1.g wet wt-1 3 h after UN (P less than 0.002); 1 wk later the remaining kidney weight had increased from 0.38 to 0.46% body weight (P less than 0.001). Renal concentration of putrescine, the product of ODC's decarboxylation of ornithine, was increased 3, 8, and 48 h after UN, but concentrations of polyamines synthesized later in the pathway, spermidine and spermine, were not appreciably affected. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, as a 1% drinking water solution inhibited both base-line renal ODC activity and putrescine concentration as well as increases stimulated by UN, although concentrations of spermidine and spermine were not decreased. In these rats, CRH still occurred, since kidney weight increased from 0.36 to 0.46% (P less than 0.001). A 2% DFMO solution caused depletion of all three polyamines, but CRH took place nevertheless. In hypophysectomized rats, both increased renal ODC activity and CRH occurred as well, indicating that these two consequences of UN do not require intact pituitary function. Although increased renal ODC activity and CRH after UN are correlated in normal and hypophysectomized rats, CRH takes place in rats treated with DFMO despite inhibition of ODC activity and depletion of polyamines.(ABSTRACT TRUNCATED AT 250 WORDS)
通过将肾鸟氨酸脱羧酶(ODC)活性和多胺含量与肾重量(以占体重的百分比表示)相关联,我们确定了ODC在代偿性肾肥大(CRH)中的作用,肾重量是在单侧肾切除(UN)1周后测定的。在正常大鼠中,UN后3小时肾ODC活性从11.0±7.4(标准差)增加到36.7±15.4 pmol 14CO2·min-1·g湿重-1(P<0.002);1周后,剩余肾脏重量从占体重的0.38%增加到0.46%(P<0.001)。鸟氨酸经ODC脱羧生成的腐胺的肾浓度在UN后3小时、8小时和48小时升高,但该途径后期合成的多胺亚精胺和精胺的浓度未受到明显影响。用ODC的不可逆抑制剂二氟甲基鸟氨酸(DFMO)以1%的饮水溶液进行预处理,可抑制基础肾ODC活性和腐胺浓度以及UN刺激引起的升高,尽管亚精胺和精胺的浓度未降低。在这些大鼠中,CRH仍然发生,因为肾脏重量从0.36%增加到0.46%(P<0.001)。2%的DFMO溶液导致所有三种多胺耗竭,但CRH仍然发生。在垂体切除的大鼠中,肾ODC活性增加和CRH也都出现,这表明UN的这两个后果不需要完整的垂体功能。尽管在正常和垂体切除的大鼠中,UN后肾ODC活性增加和CRH相关,但在DFMO处理的大鼠中,尽管ODC活性受到抑制且多胺耗竭,CRH仍然发生。(摘要截断于250字)