Phorbol 12,13-dibutyrate increases vascular tone but has a dual action on intracellular calcium levels in porcine coronary arteries

Abstract

The effects of phorbol 12,13-dibutyrate (PDBu). a protein kinase C activator, on the tone and intracellular calcium level (Cai2+) of vascular smooth muscles were simultaneously measured by use of a force-displacement transducer and the fura-2 microscopic fluorometric technique in porcine coronary arteries. Cumulatively applied PDBu produced a slowly developing and concentration-dependent contraction in the concentration range of 10(-8)-10(-6) mol/l. Contractions induced by PDBu were sustained after removal of PDBu. Changes in Cai2+ produced by PDBu were very slight, although Cai2+ was increased at lower concentrations (3 x 10(-8) and 10(-7) mol/l) and decreased at higher concentrations (3 x 10(-7) and 10(-6) mol/l). Verapamil 10(-6) mol/l partially inhibited the contractions throughout the concentration range of PDBu and the increase in Cai2+ induced by lower concentrations of PDBu. When the effects of PDBu were compared with those of the 90 mmol/l KCl medium, the force of contraction induced by a single concentration of 10(-7) mol/l PDBu was about 50% and the increase in Cai2+ was about 10%. Removal of extracellular calcium by 1 mmol/l EGTA decreased Cai2+ by about 20% but vascular tone did not change. PDbu (10(-7) mol/l) produced a small contraction without an increase in Cai2+ in the Ca2+-free medium. Depolarization by the 20 mmol/l KCl medium increased Cai2+ by about 20%, whereas vascular tone did not change.(ABSTRACT TRUNCATED AT 250 WORDS)