12-Deoxyphorbol 13-isobutyrate contracts isolated rat thoracic arteries

The vasocontractile effect of 12-deoxyphorbol 13-isobutyrate (DPB), an activator of protein kinase C (PKC), was studied to clarify the mechanism of the vascontractile response elicited by activation of PKC. DPB induced both a sustained increase in intracellular Ca2+ levels and contraction in isolated rat thoracic artery. For a given increase in intracellular Ca2+ levels. DPB induced a greater contraction than high K+ or ionomycin. In Ca(2+)-free media, DPB induced concentration-dependent contraction with a slow rate of rise without causing detectable changes in intracellular Ca2+ levels. The DPB-induced contractions in Ca(2+)-free media were less inhibited by the inhibitors of calmodulin or myosin light chain kinase than ionomycin-induced contractions in normal media were. These results indicate that activation of PKC might increase the Ca2+ sensitivity of contractile elements due to mechanisms not associated with the Ca(2+)-calmodulin pathway.