Weikel C S, Sando J J, Guerrant R L
J Clin Invest. 1985 Dec;76(6):2430-5. doi: 10.1172/JCI112258.
Microbial toxins act through cyclic nucleotide dependent (cAMP or cGMP) or cyclic nucleotide independent pathways to cause intestinal ion secretion. To explore the calcium dependent, cyclic nucleotide independent pathway that is postulated to involve protein kinase C activation, we measured protein kinase C activity and phorbol ester binding in isolated intestinal epithelial cells and examined the effects of the C-kinase activators, phorbol myristate acetate, phorbol dibutyrate, and 4-beta-phorbol-12,13-didecanoate, in weaned pig jejunum in vivo. We demonstrated both protein kinase C activity and specific phorbol ester binding in porcine jejunal epithelial cells. Phorbol myristate acetate, phorbol dibutyrate, and 4-beta-phorbol-12,13-didecanoate (10(-5) M) each caused striking secretory responses at 5 h with accumulation of Na+, K+, Cl-, and HCO3- intraluminally. In contrast, 4-alpha-phorbol and 4-alpha-phorbol-12,13-didecanoate, which do not affect protein kinase C, allowed normal net absorption of all electrolytes from the intestinal lumen equivalent to controls with only Ringer's lactate. Time course studies revealed significant secretion within 30 min after exposure to the C-kinase activators. These data suggest an important role for protein kinase C activation in intestinal ion secretion.
微生物毒素通过环核苷酸依赖性（环磷酸腺苷或环磷酸鸟苷）或环核苷酸非依赖性途径引起肠道离子分泌。为了探索钙依赖性、环核苷酸非依赖性途径（该途径被认为涉及蛋白激酶C激活），我们测量了分离的肠上皮细胞中的蛋白激酶C活性和佛波酯结合，并在断奶仔猪空肠中体内研究了C激酶激活剂佛波醇肉豆蔻酸酯乙酸盐、佛波醇二丁酸盐和4-β-佛波醇-12,13-二癸酸盐的作用。我们在猪空肠上皮细胞中证实了蛋白激酶C活性和特异性佛波酯结合。佛波醇肉豆蔻酸酯乙酸盐、佛波醇二丁酸盐和4-β-佛波醇-12,13-二癸酸盐（10⁻⁵ M）在5小时时均引起显著的分泌反应，管腔内Na⁺、K⁺、Cl⁻和HCO₃⁻积累。相比之下，不影响蛋白激酶C的4-α-佛波醇和4-α-佛波醇-12,13-二癸酸盐允许从肠腔正常净吸收所有电解质，相当于仅用乳酸林格液处理的对照组。时间进程研究显示，暴露于C激酶激活剂后30分钟内出现显著分泌。这些数据表明蛋白激酶C激活在肠道离子分泌中起重要作用。
