STIMULATION OF ENTEROCYTE PROTEIN-KINASE-C BY LAXATIVES INVITRO

To elucidate the role of protein kinase C in the mechanism of action of stimulatory laxatives, experiments were performed with preparations of rat lysed enterocytes. The phorbol ester 4-beta-phorbol 12-myristate 13-acetate (PMA) concentration-dependently (2-200 mug mL-1) stimulated the activity of protein kinase C in this preparation. Ricinoleic acid, the active principle of castor oil, deacetylbisacodyl, the active principle of bisacodyl, and deoxycholic acid exerted the same effect, although less efficiently. This reflects their potency for inducing intestinal fluid secretion and prostaglandin release, effects that are also induced more potently by PMA. Accordingly, the potency of the three C18 fatty acids, ricinoleic acid, stearic acid and oleic acid on protein kinase C activity in-vitro, on prostaglandin E2 release and on net fluid secretion in-vivo runs in parallel. It is therefore concluded that stimulatory laxatives activate protein kinase C, leading to prostaglandin E2 release, thus resulting in net fluid secretion.