Chobanian M C, Hammerman M R
Am J Physiol. 1987 Jun;252(6 Pt 2):F1073-9. doi: 10.1152/ajprenal.1987.252.6.F1073.
To characterize the regulation of ammoniagenesis and gluconeogenesis in renal proximal tubule, ammonia and glucose productions were measured in suspensions of canine proximal tubular segments incubated with 10 mM L-glutamine. Productions were linear functions of time for 120 min and were decreased as extracellular pH was increased from 7.0 to 7.5 To ascertain whether activation of protein kinase c affects either process, we incubated segments with tumor-promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate (TPA), or phorbol 12,13-dibutyrate, or with the inactive phorbol ester 4 alpha-phorbol. Ammoniagenesis and gluconeogenesis were inhibited by incubation with 10(-6) M of the two former compounds but not the latter compound. Inhibition of ammoniagenesis and gluconeogenesis occurred after incubation with as little as 10(-9) M phorbol 12,13-dibutyrate. Phorbol ester-induced inhibition was observed under conditions such that extracellular [Na+] was greater than intracellular [Na+], but not when extracellular [Na+] equaled intracellular [Na+], and was not observed in the presence of amiloride. Our findings are consistent with a role for protein kinase c in the control of ammoniagenesis and gluconeogenesis in proximal tubule. Such control could be mediated via stimulation of Na+-H+ exchange.
为了描述肾近端小管中氨生成和糖异生的调节机制，我们在含有10 mM L-谷氨酰胺的犬近端小管节段悬浮液中测量了氨和葡萄糖的生成量。生成量在120分钟内呈时间的线性函数，并且随着细胞外pH从7.0升高到7.5而降低。为了确定蛋白激酶c的激活是否影响这两个过程，我们用促肿瘤佛波酯、12-O-十四酰佛波醇-13-乙酸酯（TPA）或佛波醇12,13-二丁酸酯，或用无活性的佛波酯4α-佛波醇孵育节段。用10^(-6) M的前两种化合物孵育可抑制氨生成和糖异生，但后一种化合物则无此作用。用低至10^(-9) M的佛波醇12,13-二丁酸酯孵育后，氨生成和糖异生受到抑制。在细胞外[Na+]大于细胞内[Na+]的条件下观察到佛波酯诱导的抑制作用，但当细胞外[Na+]等于细胞内[Na+]时则未观察到，并且在存在氨氯吡咪的情况下也未观察到。我们的发现与蛋白激酶c在近端小管氨生成和糖异生控制中的作用一致。这种控制可能通过刺激Na+-H+交换来介导。
