UREA SYNTHESIS FROM AMMONIA IN PERIPORTAL AND PERICENTRAL REGIONS OF THE LIVER LOBULE - EFFECT OF OXYGEN
UREA SYNTHESIS FROM AMMONIA IN PERIPORTAL AND PERICENTRAL REGIONS OF THE LIVER LOBULE - EFFECT OF OXYGEN
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DOI：
10.1111/j.1432-1033.1987.tb10728.x
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发表时间：
1987-02-16
期刊：
影响因子：
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通讯作者：
THURMAN, RG
中科院分区：
文献类型：
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作者：
KARI, FW;YOSHIHARA, H;THURMAN, RG
用微型O2电极测量灌流NH4Cl时所消耗的额外O2，并用微型光导检测NADPH荧光的减少，以测定灌流苯巴比妥大鼠肝脏门脉周围和中心周围区域的尿素合成率。在含乳酸(5 MM)、鸟氨酸(2 MM)和谷氨酰胺合成酶抑制剂蛋氨酸亚硫胺(0.15 mM)的大鼠肝脏灌流中，以0.24 mM~3.0 mM的NH4Cl分步注入刺激尿素合成。随着NH4Cl浓度的增加，NADPH荧光强度的降低与尿素产量之间有很好的相关性(r=0.92)。通过将微型氧电极放置在肝脏表面小叶的门静脉周围或中心周围区域，停止血流并测量氧分压的下降，来确定小叶下摄氧率。根据这些测量结果，计算了存在和不存在NH4Cl时的局部O2吸收速率，以及存在NH4Cl时消耗的额外O2以及O2吸收和尿素形成之间的化学计量比，计算了局部尿素合成速率。用显微光导测量各部位注射NH4Cl引起的NADPH荧光下降的分数和整个器官的尿素合成速率，以估算尿素合成速率。当灌流方向为顺行时，根据荧光变化计算出尿素合成的最大速率为177。31mmolg-1h-1和61.+-。24微克分子g-1h-1，分别位于门静脉周围和中心周围。然而，当灌注方向为逆行时，比率为76.+-。23微克分子g-1小时-1在门静脉周围和152。19微克分子g-1小时-1在中心周围区域。在顺行方向的灌流过程中，尿素合成(通过O2摄取的变化计算)为307。+-。76微克分子g-1小时-1和72+-1。34微克分子·克~(-1)小时~(-1)，在中心周区。逆行灌流时，尿素的合成速率为54.+-。17微克分子g-1小时-1和387+-1。门静脉周围和中心周围分别为99u.molg-1h-1。因此，尿素合成的最大速率取决于灌流方向。此外，当每克肝脏的流量增加时，门脉周围区域的尿素合成率显著增加(例如，307vs.177.这些结果表明，当血流呈生理顺行方向时，肝小叶门脉周围区域合成尿素的能力最大。相反，当流动方向相反时，尿素合成的主要位置可以迅速转移到中心周围区域。因此，在灌流的肝脏中，尿素合成的最大速率是在肝小叶氧气压力最高的区域观察到的。
Rates of urea synthesis were determined in periportal and pericentral regions of the liver lobule in perfused liver from fed, phenobarbital-treated rats by measuring the extra O2 consumed upon infusion of NH4Cl with miniature O2 electrodes and from decreases in NADPH fluorescence detected with micro-light-guides. Urea synthesis by the perfused rat liver supplemented with lactate (5 mM), ornithine (2 mM) and methionine sulfoximine (0.15 mM), an inhibitor of glutamine synthetase, was stimulated by stepwise infusion of NH4Cl at doses ranging from 0.24 mM to 3.0 mM. A good correlation (r = 0.92) between decreases in NADPH fluorescence and urea production was observed when the NH4Cl concentration was increased. Sublobular rates of O2 uptake were determined by placing miniature oxygen electrodes on periportal or pericentral regions of the lobule on the liver surface, stopping the flow and measuring decreases in oxygen tension. From such measurements local rates of O2 uptake were calculated in the presence and absence of NH4Cl and local rates of urea synthesis were calculated from the extra O2 consumed in the presence of NH4 Cl and the stoichiometry between O2 uptake and urea formation. Rates of urea synthesis were also estimated from the fractional decrease in NADPH fluorescence, caused by NH4Cl infusion in each region, measured with microlight-guides and the rate of urea synthesis by the whole organ. When perfusion was in the anterograde direction, maximal rates of urea synthesis, calculated from changes in fluorescence, were 177 .+-. 31 .mu.mol g-1 h-1 and 61 .+-. 24 .mu.mol g-1 h-1 in periportal and pericentral regions, respectively. When perfusion was in the retrograde direction, however, rates were 76 .+-. 23 .mu.mol g-1 h-1 in periportal areas and 152 .+-. 19 .mu.mol g-1 h-1 in pericentral regions. During perfusion in the anterograde direction, urea synthesis, calculated by changes in O2 uptake, was 307 .+-. 76 .mu.mol g-1 h-1 and 72 .+-. 34 .mu.mol g-1 h-1 and in pericentral regions, respectively. When prefusion was in the retrograde direction, urea was synthesized at rates of 54 .+-. 17 .mu.mol g-1 h-1 and 387 .+-. 99 .mu.mol g-1 h-1 in periportal and pericentral regions, respectively. Thus, maximal rates of urea synthesis were dependent upon the direction of perfusion. In addition, rates of urea synthesis were elevated dramaticaly in periportal regions when the flow rate per gram liver was increased (e.g. 307 versus 177 .mu.mol g-1 h-1). These results demonstrate that periportal regions of the liver lobule have a greater maximal capacity to synthesize urea when flow is in the physiological anterograde direction. In contrast, the primary site of urea synthesis can be shifted rapidly to pericentral regions when the direction of flow is reversed. Thus, maximal rates of urea synthesis in the perfused liver are observed in regions of the liver lobule with the highest O2 tensions.