PENTOBARBITAL AFFECTS TRANSEPITHELIAL ELECTROPHYSIOLOGICAL PARAMETERSREGULATED BY PROTEIN-KINASE-C IN RAT DISTAL COLON

For rat distal colon, the transepithelial electrical parameters, short circuit current (I-scc) and transepithelial electrical resistance (TE R), respectively, measure net transepithelial electrolyte transport ac tivity and the barrier function of the epithelium. Studies with a vari ety of epithelial cell cultures have shown greater than 90% decreases of TER within minutes of exposure of in vitro cell sheets to phorbol e sters. The phorbol ester and protein kinase C (PKC) activator, phorbol dibutyrate (PDBU), was observed to produce an over 100% elevation of I-scc but only a small yet significant 20-30% decrease of TER across r at distal colon. Inhibition of the above effects of PDBU by the PKC in hibitor bisindolylmaleimide (GFX) is further evidence that in rat dist al colon, I-scc and TER are under regulatory control by PKC. When anim als received anesthesia with intraperitoneal pentobarbital prior to re moval of the colon, the effect of PDBU on I-scc was significantly redu ced, and the effect of PDBU on TER was almost completely inhibited. Th is effect of pentobarbital on PKC-mediated transepithelial permeabilit y parameters is consistent with the known ability of anesthetics to al ter protein kinase C activity. Exposure of rat colon to pentobarbital produced as much as a 90% inhibition of calcium-dependent PKC activity , whereas calcium-independent activity was stimulated by as much as 35 %. Prior anesthetic use may be therefore a complicating factor in obse rving PKC-mediated effects on epithelial barrier function using epithe lial tissue models.