Extracellular Ca2+-dependent contractile action of phorbol 12,13-dibutyrate on gall bladder from guinea pig

The effects of phorbol 12,13 dibutyrate (PDBu) on the isometric tone of gall bladder strips isolated from guinea pig were investigated. PDBu caused the development of a contractile force at concentrations of 5 nM to 1 microM, which was abolished by staurosporine (30 nM). The contraction was completely inhibited in Ca2+-free solution and by pretreatment with verapamil (1 microM) or nifedipine (1 microM). A lower concentration of PDBu (1 nM) potentiated the contractile response to KCl: it increased the sensitivity, but not the reactivity of KCl-induced contraction. Ca2+-induced contraction in the solution with 15 mM KCl was significantly augmented by the pretreatment with 1 nM PDBu. However, PDBu (1 nM) affected neither Ca2+-induced contraction in the presence of Ca2+ ionophore A23187 (0.7 microM) and verapamil (1 microM) nor Ba2+-induced contraction in the Ca2+-free solution. These results suggest that activation of protein kinase C induces completely extracellular Ca2+-dependent contraction by activating the voltage-dependent Ca2+ channels in gall bladder of guinea pig.