Protein kinase C mediates increase of Ca2+ sensitivity for contraction by cholinoceptor partial agonist in ileal longitudinal muscle of guinea pig.

Abstract 1. 1. Experiments were designed to study the roles of protein kinase C in carbachol- and pilocarpine-induced contraction and the increase in cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in guinea pig ileal longitudinal muscle. 2. 2. The protein kinase C inhibitors, GF 109203X (10 μM), calphostin C (10 μM) and H-7 (10 μM), reduced the maximum of the concentration response curve produced by pilocarpine more effectively than that produced by carbachol. 3. 3. The slopes of the regression lines between [Ca 2+ ] i and tension development for pilocarpine and carbachol in tissues treated with GF 109203X were significantly gentler than those for untreated tissues. 4. 4. The protein kinase C α - and β 1 selective inhibitor Goe 6976 (1 μM) decreased both [Ca 2+ ] i and contraction, but did not affect the slopes of the regression lines for pilocarpine and carbachol. 5. 5. These results suggest that protein kinase C (both n- and/or a-type) plays an important role in the increase of Ca 2+ sensitivity of the contractile element, and that pilocarpine mainly activates the protein kinase C-dependent pathways for contractile mechanisms in guinea pig ileal longitudinal muscle.