Effects of phorbol ester on cytosolic Ca2+ levels, muscle tension and myosin phosphorylation in vascular smooth muscle

• Published in: Japanese Journal of Pharmacology 1990, Vol.52 (suppl-1.2), p.346-346
• Main Authors: Sato, Koichi, Hori, Masatoshi, Ohyama, Tatsuya, Ozaki, Hiroshi, Kato, Iwao, Karaki, Hideaki
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)55861-9

In isolated rat aorta, 12-deoxyphorbol 13-isobutyrate (DPB) increased cytosolic Ca^2+ levels ([Ca^2+ ]_i ), 20kDa myosin light chain (MLC) phosphorylation and muscle tension in the presence of external Ca^2+ . The increments in muscle tension and MLC phosphorylation due to DPB were greater than those due to high K^+ at a given [Ca^2+ ]_i . The Ca^2+ channel blockers, verapamil and nicardipine, decreased the DPB-induced increments in [Ca^2+ ]_i and MLC phosphorylation to their respective resting levels, although these inhibitors inhibited the contraction only by approximately 10%. In the absence of external Ca^2+ , DPB still induced a sustained contraction without increasing [Ca^2+ ]_i or MLC phosphorylation. In isolated rabbit mesenteric artery permeabilized with Staphylococcus aureus α-toxin, cumulative addition of Ca^2+ induced a graded contraction. In the presence of DPB, the pCa^2+ -tension curve shifted to the lower Ca^2+ levels. These results indicate that the contraction induced by phorbol ester is due to 1) the sustained increases in [Ca^2+ ]_i and MLC phosphorylation, 2) the sensitization of contractile elements to Ca^2+ which may be due to a greater MLC phosphorylation level at a given [Ca^2+ ]_i and 3) the activation of a contractile mechanism which is dependent on neither Ca^2+ nor MLC phosphorylation.