Stimulation of porcine jejunal ion secretion in vivo by protein kinase-C activators.

Abstract

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.