CONTRACTILE AND RELAXANT EFFECTS OF PHORBOL ESTER IN THE INTESTINAL SMOOTH-MUSCLE OF GUINEA-PIG TAENIA CECI

1 Effects of phorbol esters on the cytosolic Ca2+ level ([Ca2+]i) and muscle tension in the intestinal smooth muscle of guinea-pig taenia caeci were examined. 2 12-Deoxyphorbol 13-isobutyrate (DPB, 1 mum) did not change the [Ca2+]i and tension in resting muscle. 3 In high K+-stimulated muscle, 1 mum DPB transiently augmented the contraction and decreased [Ca2+]i. 12-Deoxyphorbol 13-isobutyrate 20-acetate (1 mum) and phorbol 12, 13-dibutyrate (1 mum) showed similar effects to DPB whereas phorbol 12-myristate 13-acetate (1 mum) and phorbol 12, 13-didecanoate (1 mum) were ineffective. 4 DPB (1 mum) inhibited both [Ca2+]i and tension stimulated by 300 nm carbachol or 3 mum histamine. In the presence of a higher concentration of carbachol (1 mum), DPB decreased [Ca2+]i and transiently increased muscle tension. 5 In the muscle strips permeabilized with bacterial alpha-toxin, 1 mum DPB shifted the Ca2+-tension curve to the left. An inhibitor of protein kinase C, H-7 (30 mum), inhibited the effect of DPB. 6 DPB did not change the high K+-induced contraction in the muscle strips pretreated with 3 mum phorbol 12-myristate 13-acetate for 24 h. 7 These results suggest that activation of protein kinase C has dual effects; it augments contraction by increasing the Ca2+ sensitivity of the contractile elements and it inhibits contraction by decreasing [Ca2+]i.