Protein kinase C and intestinal fluid secretion: involvement of prostaglandin E 2 but not of 5-hydroxytryptamine

Abstract

To determine the role of protein kinase C in the regulation of intestinal fluid transport, experiments were performed with the rat jejunum in vivo, using the active phorbol ester, 4-β-phorbol 12-myristate 13-acetate (PMA), as stimulator of protein kinase C. Intraluminally administered PMA dose dependently reversed the net fluid absorption to net fluid secretion and significantly increased prostaglandin E 2 (PGE 2) but not 5-hydroxytryptamine (5-HT) output into the lumen. Mucosal cyclic AMP levels remained unchanged by PMA. Indomethacin inhibited the increase in PGE 2 output and partially reduced the secretory response to PMA. Ketanserin was without effect whereas verapamil totally blocked the secretory response to PMA. It is concluded that intestinal fluid secretion, stimulated by activation of protein kinase C is partly mediated by PGE 2 release. PGE 2 may facilitate calcium entry rather than increase intracellular calcium through activation of cyclic AMP. Protein kinase C appears to play an important role as an intermediate in phosphoinositol hydrolysis, which is initiated by 5-HT, and finally induces fluid secretion via PGE 2.